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id="submitall">SUBMIT ALL</string><string id="acc_submitall">submit all</string><string id="question_list">Question List</string><string id="more_info">More info</string><string id="send_an_email">Send an email</string><string id="close">Close</string><string id="bio">Bio</string><string id="exit">Exit</string></string_table></string_tables><sounds enabled="false" /><nav_data><outline><links><slidelink slideid="_player.61n27wxgV0X.5u2Q2nQJNSs" displaytext="Development of B cells " expand="true" type="slide"><links><slidelink slideid="_player.61n27wxgV0X.5pcDo7bZ9a3" displaytext="Comparison of the Properties of B-1 Cells and B-2 Cells" expand="true" type="slide" /></links></slidelink><slidelink slideid="_player.61n27wxgV0X.5hWLUY1OtzG" displaytext="Introduction to the Six Phases of B Cell Development" expand="true" type="slide"><links><slidelink slideid="_player.61n27wxgV0X.6RfJXJNynL6" displaytext="The Six Phases of B Cell Development" expand="true" type="slide" /><slidelink slideid="_player.61n27wxgV0X.5zceSljzYgX" displaytext="Phases 1 to 3" expand="true" type="slide" /><slidelink slideid="_player.61n27wxgV0X.6TuVJrj6LiX" displaytext="Migration of Naïve Mature B Cells Expressing Surface IgM and IgD Antibodies to Secondary Lymphoid Organs and Tissues" expand="true" type="slide" /><slidelink slideid="_player.61n27wxgV0X.5kEk1kmgsuC" displaytext="Phases 4 to 6" expand="true" type="slide" /></links></slidelink><slidelink slideid="_player.61n27wxgV0X.6SytZbtQadw" displaytext="B Cells undergo 5 stages " expand="true" type="slide"><links><slidelink slideid="_player.61n27wxgV0X.6FcoTlDE6mi" displaytext="The Five Stages of B Cell &#xD;Development in the Bone Marrow" expand="true" type="slide" /><slidelink slideid="_player.61n27wxgV0X.6SQddVcuQtT" displaytext="Expression of CD Markers at Various &#xD;Developmental Stage of B Cells" expand="true" type="slide" /><slidelink slideid="_player.61n27wxgV0X.6auDiX4RFB4" displaytext="Stages of B Cell Development are Defined by The Arrangement and Expression of the Immunoglobulin Genes" expand="true" type="slide" /><slidelink slideid="_player.61n27wxgV0X.6XTcrm3klrA" displaytext="Early Stages of B Cell Development are&#xD;Dependent on Bone Marrow Stromal Cells" expand="true" type="slide" /><slidelink slideid="_player.61n27wxgV0X.5il4wnLoT99" displaytext="Immunoglobulin Heavy Chain Rearrangement in Pro-B Cells May Result in Productive or Nonproductive Rearrangements" expand="true" type="slide" /><slidelink slideid="_player.61n27wxgV0X.61A1ndMFDLM" displaytext="Pre-B-cell Receptor Resembles the B-cell Receptor in Structure, but not in Composition" expand="true" type="slide" /><slidelink slideid="_player.61n27wxgV0X.5jq6VHO4tSg" displaytext="Description of Iga:Igb Dimer and its Association with BCR" expand="true" type="slide" /><slidelink slideid="_player.61n27wxgV0X.6oRIOoXw1zd" displaytext="Nonproductive Light Chain Gene Rearrangements can be Superseded by Further Gene Rearrangement" expand="true" type="slide" /><slidelink slideid="_player.61n27wxgV0X.5Xm9u3McP4p" displaytext="Rearrangement of the Immunoglobulin Light-chain Genes in Pre-B Cells Leads to the Expression of Cell-Surface IgM " expand="true" type="slide" /><slidelink slideid="_player.61n27wxgV0X.5lA99ZRNkPv" displaytext="There are Two Fate-determining Checkpoints During B-Cell Development in the Bone Marrow " expand="true" type="slide" /><slidelink slideid="_player.61n27wxgV0X.5rBBn6SaEGJ" displaytext="Order of Gene Rearrangements that Lead to the Expression of Cell-surface Immunoglobulin " expand="true" type="slide" /><slidelink slideid="_player.61n27wxgV0X.6Pc9lguzVs3" displaytext="Recap" expand="true" type="slide" /></links></slidelink><slidelink slideid="_player.61n27wxgV0X.6Bpv3iqsn42" displaytext="Negative and Positive Selection of B Cells for Maturation" expand="true" type="slide"><links><slidelink slideid="_player.61n27wxgV0X.6YL4jZIVsHA" displaytext="Immature B Cells with Specificity for Multivalent Self- Antigens are Retained in the Bone Marrow" expand="true" type="slide" /><slidelink slideid="_player.61n27wxgV0X.5g2QRSzgzsh" displaytext="By Changing their Antigen Specificities Receptor Editing Rescues Many Self-reactive B Cells" expand="true" type="slide" /><slidelink slideid="_player.61n27wxgV0X.5xabYIz7RRk" displaytext="Immature B Cells Specific for Monovalent Self-antigens Develop a State of Anergy" expand="true" type="slide" /><slidelink slideid="_player.61n27wxgV0X.6kCXr0IVvX5" displaytext="Recap" expand="true" type="slide" /><slidelink slideid="_player.61n27wxgV0X.6rj4gaMK6Rs" displaytext="The General Route of B-cell Circulation Through a Lymphoid Tissue" expand="true" type="slide" /><slidelink slideid="_player.61n27wxgV0X.6iBNRezjt0K" displaytext="Immature B Cells Must Pass Through a Primary Follicle in a Secondary Lymphoid Tissue to Become Mature B Cells " expand="true" type="slide" /><slidelink slideid="_player.61n27wxgV0X.5bihUeDAiy7" displaytext="The Dendrites of Follicular Dendritic Cells Take Up Intact Pathogens and Antigens and Preserve Them for Long Periods" expand="true" type="slide" /><slidelink slideid="_player.61n27wxgV0X.6LXX1gcCEMU" displaytext="Naïve B Cells Recognize Antigens Captured by Subcapsular Sinus Macrophages and Follicular dendritic Cells (FDCs)" expand="true" type="slide" /><slidelink slideid="_player.61n27wxgV0X.5a3OXKnhdoP" displaytext="B cells Activated by Antigen in the B-cell Area Move to the Area Boundary, Where They are Helped by Antigen-Specific Effector Tfh Cells Coming from the T Cell Area" expand="true" type="slide" /><slidelink slideid="_player.61n27wxgV0X.5VAmtXMaQG8" displaytext="Summary of the Main Stages in B-cell Development" expand="true" type="slide" /><slidelink slideid="_player.61n27wxgV0X.5wZF0MG7XHD" displaytext="Recap" expand="true" type="slide" /></links></slidelink></links></outline></nav_data><resource_data description="" /><transcript_data><slidetranscripts><slidetranscript slideid="61n27wxgV0X.5u2Q2nQJNSs" slidebank="false" type="slide" noteswf="" /><slidetranscript slideid="61n27wxgV0X.5pcDo7bZ9a3" slidebank="false" type="slide" noteswf="story_content/notes/Note61n27wxgV0X.5pcDo7bZ9a3.swf">&lt;html&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt;B-1 cells develop in the omentum, a part of the peritoneum, as well as in fetal liver; and are produced by the bone marrow only for a short period around the time of birth. &lt;/font&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt;A pool of self-renewing B-1 cells is then established, which does not require the microenvironment of the bone marrow for its survival. &lt;/font&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt;B-1 cells are distinguished from other B cells by the presence of CD5, hence they are also called CD5 B cells. These cells produce antibodies mainly of the IgM class against common bacterial polysaccharides and other carbohydrates. Antibodies to proteins are negligible &lt;/font&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt;The limited diversity of the antibodies made by B-1 cells and their tendency to be polyspecific and of low affinity suggests that B-1 cells produce a simpler, less adaptive immune response than that involving B-2 cells.&lt;/font&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt;Conventionally B-2 cells are simply referred to as B cells.&lt;/font&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;/html&gt;</slidetranscript><slidetranscript slideid="61n27wxgV0X.5hWLUY1OtzG" slidebank="false" type="slide" noteswf="" /><slidetranscript slideid="61n27wxgV0X.6RfJXJNynL6" slidebank="false" type="slide" noteswf="story_content/notes/Note61n27wxgV0X.6RfJXJNynL6.swf">&lt;html&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt;Let’s consider first a big picture of the various phases that B cells have to go through in order to carry out their functions.&lt;/font&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt;The first three phases that are shown  correspond to B development in the bone marrow.&lt;/font&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt;The last three phases that are shown correspond to B cell development in the secondary lymphoid tissues. &lt;/font&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;/html&gt;</slidetranscript><slidetranscript slideid="61n27wxgV0X.5zceSljzYgX" slidebank="false" type="slide" noteswf="story_content/notes/Note61n27wxgV0X.5zceSljzYgX.swf">&lt;html&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt;These are the first three phases of B cell development, including repertoire assembly, negative selection and positive selection.&lt;/font&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt;In phase 1, immature B cells with surface IgM are generated by rearrangement of the heavy chain gene, followed by that of the&lt;/font&gt;&lt;font face='Symbol' size='12.5pt' color='#ffffff'&gt; &lt;/font&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt;light chain gene, or &lt;/font&gt;&lt;font face='Symbol' size='12.5pt' color='#ffffff'&gt;&lt;/font&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt; in case of failure in &lt;/font&gt;&lt;font face='Symbol' size='12.5pt' color='#ffffff'&gt; &lt;/font&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[48, 96, 144]' blockindent='0' indent='0'&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt;light chain gene rearrangement.&lt;/font&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[48, 96, 144]' blockindent='0' indent='0'&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt;In phase 2, immature B cells with surface IgMs that bind to normal surface constituents in the human body are retained in the bone marrow and allowed to rearrange the light chain gene again, as many times as the number of J gene segments available, and on both chromosomes if all attempts in the first chromosome fail.   &lt;/font&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt;If these cells fail to express surface IgM molecules that no longer bind to surface components of the host cells, they are eliminated by apoptosis. &lt;/font&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt;In phase 3, the immature B Cells that do not bind to components of the host cell self-surface antigens in the bone marrow are allowed to mature, and the cells expressing both surface IgM and IgD antibodies are released into the blood circulation.&lt;/font&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;/html&gt;</slidetranscript><slidetranscript slideid="61n27wxgV0X.6TuVJrj6LiX" slidebank="false" type="slide" noteswf="story_content/notes/Note61n27wxgV0X.6TuVJrj6LiX.swf">&lt;html&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt;Mature B cells leaving the bone marrow (colored in yellow) are carried in the blood to the lymph nodes, spleen, Peyer’s patches (colored in red), and other secondary lymphoid tissues such as those lining the respiratory tract; which is not shown in this diagram. &lt;/font&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;/html&gt;</slidetranscript><slidetranscript slideid="61n27wxgV0X.5kEk1kmgsuC" slidebank="false" type="slide" noteswf="story_content/notes/Note61n27wxgV0X.5kEk1kmgsuC.swf">&lt;html&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt;In phase 4, naïve mature B cells recirculate between the blood and the lymph and through secondary lymphoid tissues in search of infection and pathogen-derived antigens.&lt;/font&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt;In phase 5, B cells that bind to pathogen-derived antigens undergo activation and clonal expansion.&lt;/font&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt;In phase 6, B cells generated from clonal expansion undergo differentiation into effector plasma cells and memory cells.  &lt;/font&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt;Antibodies produced by plasma cells carry out their functions as described in previous lectures.  &lt;/font&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;/html&gt;</slidetranscript><slidetranscript slideid="61n27wxgV0X.6SytZbtQadw" slidebank="false" type="slide" noteswf="" /><slidetranscript slideid="61n27wxgV0X.6FcoTlDE6mi" slidebank="false" type="slide" noteswf="story_content/notes/Note61n27wxgV0X.6FcoTlDE6mi.swf">&lt;html&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt;This diagram is an introduction to the development of B cells.&lt;/font&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt;Each phase is determined by a step in the rearrangement of the immunoglobulin gene segments, and by the expression of differentiation cell surface molecules.&lt;/font&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;/html&gt;</slidetranscript><slidetranscript slideid="61n27wxgV0X.6SQddVcuQtT" slidebank="false" type="slide" noteswf="story_content/notes/Note61n27wxgV0X.6SQddVcuQtT.swf">&lt;html&gt;&lt;p align='left'&gt;&lt;textformat leading='2' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt;Cells at different stages of development are identified by different combinations of CD proteins on their surface. &lt;/font&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='2' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt;CD34 is expressed in hematopoietic stem cell&lt;/font&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='2' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt;CD10 is expressed in common lymphoid progenitor&lt;/font&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='2' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt;CD127 is the &lt;/font&gt;&lt;font face='Symbol' size='12.5pt' color='#ffffff'&gt;&lt;/font&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt; chain of the receptor for interleukin-7, which is an important cytokine in the development of stem cells into B cell precursors.&lt;/font&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='2' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt;Note that the difference between pro-B cells and B cell precursor is the expression of CD19 in pro-B cells. CD19 will later be shown to play a role in signal transduction in mature B cells.&lt;/font&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;/html&gt;</slidetranscript><slidetranscript slideid="61n27wxgV0X.6auDiX4RFB4" slidebank="false" type="slide" noteswf="story_content/notes/Note61n27wxgV0X.6auDiX4RFB4.swf">&lt;html&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt;In the stem cell, the immunoglobulin genes are in the germline configuration. &lt;/font&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt;The first rearrangements are of the heavy-chain genes. Joining DH to JH defines the early pro-B cell, which becomes a late pro-B cell on joining VH to DJH.&lt;/font&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt;Expression of a functional μ chain defines the large pre-B cell. Large pre-B cells proliferate, producing small pre-B cells in which rearrangement of the light-chain gene occurs.&lt;/font&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt;Successful light-chain gene rearrangement and expression of IgM molecules on the cell surface define the immature B cell. &lt;/font&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt;It is noteworthy that after the completion of the heavy chain VDJ recombination, the &lt;/font&gt;&lt;font face='Symbol' size='12.5pt' color='#ffffff'&gt;&lt;/font&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt; chain is expressed in association with a pseudo or surrogate light chain at the surface of the small pre-B cell, while the &lt;/font&gt;&lt;font face='Symbol' size='12.5pt' color='#ffffff'&gt;&lt;/font&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt; light chain is recombining a V gene segment to a J gene segment.&lt;/font&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;/html&gt;</slidetranscript><slidetranscript slideid="61n27wxgV0X.6XTcrm3klrA" slidebank="false" type="slide" noteswf="story_content/notes/Note61n27wxgV0X.6XTcrm3klrA.swf">&lt;html&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt;These images show the interactions of developing B cells with bone marrow stromal cells.  Pro-B cell VLA-4 binding to VCAM on stroma cells facilitates subsequent interactions.   Binding of B cell Kit to stem cell factor, abbreviated as SCF, causes Pro-B cells to proliferate.  At a later stage of maturation stromal cells produce IL-7 which acts on late pro-B cell, driving its maturation to pre-B cell. &lt;/font&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;/html&gt;</slidetranscript><slidetranscript slideid="61n27wxgV0X.5il4wnLoT99" slidebank="false" type="slide" noteswf="story_content/notes/Note61n27wxgV0X.5il4wnLoT99.swf">&lt;html&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt;The heavy chain gene is rearranged on the first chromosome 14, and if unsuccessful on the second chromosome 14.&lt;/font&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt;If neither rearrangement is successful, the cell dies by apoptosis.&lt;/font&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt;A productive rearrangement is necessary for the pro-B cell to proceed to the next stage of development. Of course without a heavy chain, there is no need to rearrange the light chain gene segments.&lt;/font&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;/html&gt;</slidetranscript><slidetranscript slideid="61n27wxgV0X.61A1ndMFDLM" slidebank="false" type="slide" noteswf="story_content/notes/Note61n27wxgV0X.61A1ndMFDLM.swf">&lt;html&gt;&lt;p align='left'&gt;&lt;textformat leading='2' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt;This image illustrates the structure of the &lt;/font&gt;&lt;font face='Symbol' size='12.5pt' color='#ffffff'&gt;&lt;/font&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt; chain with the associated surrogate light chain, and the association of this complex with the Ig&lt;/font&gt;&lt;font face='Symbol' size='12.5pt' color='#ffffff'&gt;&lt;/font&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt; and Ig&lt;/font&gt;&lt;font face='Symbol' size='12.5pt' color='#ffffff'&gt; &lt;/font&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt;dimer which is important to signal transduction.&lt;/font&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='2' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt;Distinguishing the pre-B-cell receptor from the B-cell receptor is the absence of a κ or λ immunoglobulin light chain, and the presence instead of the surrogate light chain composed of the VpreB and λ5 polypeptides, which also transduce the signal necessary for pre-B-cell survival.&lt;/font&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='2' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt;It is noteworthy that both the pre-B cell receptor and B-cell receptor are associated with Ig&lt;/font&gt;&lt;font face='Symbol' size='12.5pt' color='#ffffff'&gt;&lt;/font&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt;-Ig&lt;/font&gt;&lt;font face='Symbol' size='12.5pt' color='#ffffff'&gt;&lt;/font&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt; dimer, which plays a role in signal transduction.  &lt;/font&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;/html&gt;</slidetranscript><slidetranscript slideid="61n27wxgV0X.5jq6VHO4tSg" slidebank="false" type="slide" noteswf="story_content/notes/Note61n27wxgV0X.5jq6VHO4tSg.swf">&lt;html&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt;Igα and Igβ are disulfide-linked. These molecules have long cytoplasmic tails that can interact with intracellular signaling proteins.  Thus, the complex of immunoglobulin with Igα and Igβ serves as the functional B-cell receptor. &lt;/font&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt;The immunoglobulin shown here is IgM, but all isotypes can serve as B-cell receptors.   Igα and Igβ are also called CD79a and CD79b, respectively.&lt;/font&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;/html&gt;</slidetranscript><slidetranscript slideid="61n27wxgV0X.6oRIOoXw1zd" slidebank="false" type="slide" noteswf="story_content/notes/Note61n27wxgV0X.6oRIOoXw1zd.swf">&lt;html&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt;After the heavy chain gene, the&lt;/font&gt;&lt;font face='Symbol' size='12.5pt' color='#ffffff'&gt; &lt;/font&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[48, 96, 144]' blockindent='0' indent='0'&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt;light chain gene on chromosome 2 is the next gene to be rearranged.&lt;/font&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[48, 96, 144]' blockindent='0' indent='0'&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt;Shown in this diagram is an illustration of two unsuccessful rearrangements of the &lt;/font&gt;&lt;font face='Symbol' size='12.5pt' color='#ffffff'&gt;&lt;/font&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[48, 96, 144]' blockindent='0' indent='0'&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt; light chain gene  in the recombination of  a V gene segment with a J gene segment,  followed by a successful rearrangement on a third trial.&lt;/font&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[48, 96, 144]' blockindent='0' indent='0'&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt;In consideration, of the number of J gene segments, there are up to five successive attempts at productive rearrangement. &lt;/font&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt;It is noteworthy that there are the same numbers of attempts possible in the second chromosome 2.  &lt;/font&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;/html&gt;</slidetranscript><slidetranscript slideid="61n27wxgV0X.5Xm9u3McP4p" slidebank="false" type="slide" noteswf="story_content/notes/Note61n27wxgV0X.5Xm9u3McP4p.swf">&lt;html&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt;Should all attempts in the rearrangement of the&lt;/font&gt;&lt;font face='Symbol' size='12.5pt' color='#ffffff'&gt; &lt;/font&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt; light chain gene fail, rearrangement of the &lt;/font&gt;&lt;font face='Symbol' size='12.5pt' color='#ffffff'&gt;&lt;/font&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[48, 96, 144]' blockindent='0' indent='0'&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt; light chain gene is initiated.&lt;/font&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[48, 96, 144]' blockindent='0' indent='0'&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt;This diagram is an illustration showing the sequence of the light chain gene rearrangements, and the apoptosis of the cells in which all attempts are nonproductive as shown by the red arrows.&lt;/font&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt;Productive rearrangement of the &lt;/font&gt;&lt;font face='Symbol' size='12.5pt' color='#ffffff'&gt;&lt;/font&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt; or &lt;/font&gt;&lt;font face='Symbol' size='12.5pt' color='#ffffff'&gt;&lt;/font&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt; light chain results in its association with the &lt;/font&gt;&lt;font face='Symbol' size='12.5pt' color='#ffffff'&gt;&lt;/font&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[48, 96, 144]' blockindent='0' indent='0'&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt;chains to form surface IgM on the immature B cells.&lt;/font&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[48, 96, 144]' blockindent='0' indent='0'&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;/html&gt;</slidetranscript><slidetranscript slideid="61n27wxgV0X.5lA99ZRNkPv" slidebank="false" type="slide" noteswf="story_content/notes/Note61n27wxgV0X.5lA99ZRNkPv.swf">&lt;html&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt;This figure shows the two fate-determining check points during B cell development in the bone marrow.&lt;/font&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt;The first check point is whether a functional heavy chain has been produced&lt;/font&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt;The second check point is whether a functional light chain has been produced.&lt;/font&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt;Cells that fail either of these checkpoints are eliminated by apoptosis.&lt;/font&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;/html&gt;</slidetranscript><slidetranscript slideid="61n27wxgV0X.5rBBn6SaEGJ" slidebank="false" type="slide" noteswf="story_content/notes/Note61n27wxgV0X.5rBBn6SaEGJ.swf">&lt;html&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt;This is a composite diagram of immunoglobulin gene rearrangements. &lt;/font&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt;Developing B cells are allowed to proceed to the next stage only when a productive rearrangement has been made. &lt;/font&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt;If a nonproductive rearrangement is made on one chromosome of a homologous pair, then rearrangement is attempted on the second chromosome. &lt;/font&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;/html&gt;</slidetranscript><slidetranscript slideid="61n27wxgV0X.6Pc9lguzVs3" slidebank="false" type="slide" noteswf="" /><slidetranscript slideid="61n27wxgV0X.6QYSJT308H2" slidebank="false" type="slide" noteswf="" /><slidetranscript slideid="61n27wxgV0X.5etlp41ZhU5" slidebank="false" type="slide" noteswf="" /><slidetranscript slideid="61n27wxgV0X.6Bpv3iqsn42" slidebank="false" type="slide" noteswf="" /><slidetranscript slideid="61n27wxgV0X.6YL4jZIVsHA" slidebank="false" type="slide" noteswf="story_content/notes/Note61n27wxgV0X.6YL4jZIVsHA.swf">&lt;html&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt;The left panels show that immature B cells that are not specific for a self-antigen in the bone marrow mature further to express IgM and IgD and leave the bone marrow.&lt;/font&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt;The right panels show that immature B cells specific for a self-antigen on bone marrow cells are retained in this tissue. &lt;/font&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;/html&gt;</slidetranscript><slidetranscript slideid="61n27wxgV0X.5g2QRSzgzsh" slidebank="false" type="slide" noteswf="story_content/notes/Note61n27wxgV0X.5g2QRSzgzsh.swf">&lt;html&gt;&lt;p align='left'&gt;&lt;textformat leading='2' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt;Binding to a self-antigen in the bone marrow causes the immature B cell to continue to rearrange its light-chain loci.&lt;/font&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='2' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt;This deletes the existing self-reactive rearrangement and may also produce a new light-chain rearrangement giving immunoglobulin that is not specific for self-antigen. &lt;/font&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='2' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt;The left panel shows that when no more rearrangements are possible the self–reactive B cell dies.&lt;/font&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='2' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt;The right panel shows that successive rearrangements occur until a new non-self-reactive rearrangement is made, and the B-cell continues its development.&lt;/font&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;/html&gt;</slidetranscript><slidetranscript slideid="61n27wxgV0X.5xabYIz7RRk" slidebank="false" type="slide" noteswf="story_content/notes/Note61n27wxgV0X.5xabYIz7RRk.swf">&lt;html&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt;This diagram illustrates that immature B cells that bind soluble univalent self-antigen are signaled to express IgD, and released into the blood circulation but that they become anergic or unresponsive and then die. &lt;/font&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;/html&gt;</slidetranscript><slidetranscript slideid="61n27wxgV0X.6kCXr0IVvX5" slidebank="false" type="slide" noteswf="" /><slidetranscript slideid="61n27wxgV0X.6rj4gaMK6Rs" slidebank="false" type="slide" noteswf="story_content/notes/Note61n27wxgV0X.6rj4gaMK6Rs.swf">&lt;html&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt;This diagram illustrates the extravasation of naïve mature B cells in the lymph node via the high endothelial venules (abbreviated as HEVs and their homing in primary follicles, or their passage through the lymph node.&lt;/font&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt;B cells circulating in the blood enter the lymph node cortex via a HEV. &lt;/font&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt;From there they migrate to a primary lymphoid follicle.&lt;/font&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt;If they do not encounter their specific antigen, they leave the follicle and exit from the lymph node via the efferent duct. &lt;/font&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt;The circulation route is the same for immature and mature B cells, which all compete with each other to enter the primary follicles. &lt;/font&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;/html&gt;</slidetranscript><slidetranscript slideid="61n27wxgV0X.6iBNRezjt0K" slidebank="false" type="slide" noteswf="story_content/notes/Note61n27wxgV0X.6iBNRezjt0K.swf">&lt;html&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt;In this diagram you can see the immature B cells enter the secondary lymphoid tissue through the walls of HEVs, attracted by the chemokines CCL21 and CCL19, and compete with other immature and mature B cells to enter a primary follicle, annotated as PF. &lt;/font&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt;Follicular dendritic cells, abbreviated as FDCs (colored turquoise), secrete the chemokine CXCL13, which attracts B cells into the primary follicle.&lt;/font&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt;Immature B cells that enter a follicle interact with proteins on FDCs that signal their final maturation into mature B cells. &lt;/font&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt;If they do not encounter their specific antigen in the follicle, mature B cells leave the lymph node and continue recirculating through the secondary lymphoid tissues via the lymph and blood. &lt;/font&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt;Immature B cells that fail to enter a follicle also continue recirculation but will soon die. &lt;/font&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;/html&gt;</slidetranscript><slidetranscript slideid="61n27wxgV0X.5bihUeDAiy7" slidebank="false" type="slide" noteswf="story_content/notes/Note61n27wxgV0X.5bihUeDAiy7.swf">&lt;html&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt;This is a scanning electron micrograph shows an FDC with a well-defined cell body and numerous dendritic processes.&lt;/font&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt;The dendrites initially have a thread-like or filiform appearance. &lt;/font&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt;When pathogens and antigens are bound to complement receptors CR1 and CR2 on the FDC surface they become clustered, forming prominent beads, designated as iccosomes, at intervals along the dendrites as seen here.&lt;/font&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt;Complement activation during the innate immune response leads to the attachment of C3b and its breakdown products as C3d.  &lt;/font&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt;C3b and C3d-tagged antigens are taken up by CR2 at the surface of FDC. &lt;/font&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt;This figure completes the overall picture of B cell activity in the lymph node and more accurately in the primary follicle.&lt;/font&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;/html&gt;</slidetranscript><slidetranscript slideid="61n27wxgV0X.6LXX1gcCEMU" slidebank="false" type="slide" noteswf="story_content/notes/Note61n27wxgV0X.6LXX1gcCEMU.swf">&lt;html&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt;Antigens tagged with Cdb and C3d are brought to the lymph node from the infected tissue in the afferent lymph. &lt;/font&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt;By binding to C3b or C3d, CR1 and CR2 on subcapsular sinus macrophages and FDCs tethers the antigen to the cell surface, where it can be screened by naive B cells arriving either from the blood via a high endothelial venule or in the afferent lymph.&lt;/font&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt;This slide illustrates the role of subcapsular sinus and FDCs in the tethering of antigens for presentation to naive B cells in the lymph node.&lt;/font&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt;This figure shows that macrophages also play a role in holding antigens for presentation to B cells.&lt;/font&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;/html&gt;</slidetranscript><slidetranscript slideid="61n27wxgV0X.5a3OXKnhdoP" slidebank="false" type="slide" noteswf="story_content/notes/Note61n27wxgV0X.5a3OXKnhdoP.swf">&lt;html&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt;In the first panel, circulating naive B and T cells are shown leaving the blood at a high endothelial venule (HEV) to enter the lymph node draining an infection. &lt;/font&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt;Myeloid dendritic cells in the T-cell area activate antigen-specific naive CD4 T cells, while in the B-cell area, which is the cortex containing the primary follicles, intact antigen represented by red dots deposited on follicular dendritic cells or FDCs is taken up by naive antigen-specific B cells and initiates their activation. &lt;/font&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt;In the second panel in the T-cell area, which is in the paracortex of the lymph node, naive T cells proliferate to become clones of effector Tfh cells. &lt;/font&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt;In the B-cell area, which is in the cortex containing primary follicles, antigen-specific B cells process endocytized antigen and present Agp: MHC-II complexes CD4 Th. &lt;/font&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt;(cont)&lt;/font&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt;These antigen-activated B cells move to the boundary region. &lt;/font&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt;In the third panel, effector Tfh cells also move to the boundary region, where they screen the Agp: MHC-II complexes presented by the antigen-activated B cells. &lt;/font&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt;Conjugates are formed between a Tfh cell and a B cell that presents its specific antigen.&lt;/font&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt;In the original paper, which demonstrates the meeting of B and Tfh cells at the boundary between the cortex and paracortex, the authors refer to this phenomenon as B and T cells “on a date”.  &lt;/font&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;/html&gt;</slidetranscript><slidetranscript slideid="61n27wxgV0X.5VAmtXMaQG8" slidebank="false" type="slide" noteswf="story_content/notes/Note61n27wxgV0X.5VAmtXMaQG8.swf">&lt;html&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt;The top panels summarize the early stages of development in the bone marrow. &lt;/font&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt;The status of the immunoglobulin heavy μ chain and κ/λ light-chain genes is shown below each panel. &lt;/font&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt;The bottom panels summarize the development of B cells after they leave the bone marrow, enter the secondary lymphoid tissues and are activated by pathogen-derived specific antigen.&lt;/font&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;p align='left'&gt;&lt;textformat leading='0' tabstops='[0, 48, 96, 144]' blockindent='0' indent='0'&gt;&lt;font face='Open Sans' size='12.5pt' color='#ffffff'&gt;Please note that this diagram refers only to the development of B-2 cells. This nomenclature is not commonly used, and these B cells are simply referred to as “B cells”.  &lt;/font&gt;&lt;/textformat&gt;&lt;/p&gt;&lt;/html&gt;</slidetranscript><slidetranscript slideid="61n27wxgV0X.5wZF0MG7XHD" slidebank="false" type="slide" noteswf="" /><slidetranscript slideid="61n27wxgV0X.6qqzWlFz7sC" slidebank="false" type="slide" noteswf="" /><slidetranscript slideid="61n27wxgV0X.6WIva8zMGXm" slidebank="false" type="slide" noteswf="" /></slidetranscripts></transcript_data><glossary_data /></bwFrame>