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b cell development

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BLG 307
Clare Chua

Outline of Lecture 04 Immunoglobulins III, B Cell Development I. Overview B Cell development has two phases (see Fig. 1, p. 59): - Antigen independent: (bone marrow), V(D)J and allelic exclusion - Antigen dependent: (elsewhere), clonal selection, class switching, hypermutation II. Antigen-Independent development of B Cells A. Occurs in the bone marrow: 1) DJ rearrangement at both heavy chain alleles (now called pro-B cell) 2) VDJ rearrangement and heavy chain expression (now pre-B cell) 3) VJ rearrangement of κ chain 4) If unsuccessful at both loci, VJ rearrangement of λ chain 5) Expression of surface IgM (now immature B cell) 6) Tolerance testing and receptor editing if anti-self 7) Migration to secondary lymphoid organs (now peripheral B cell) B. Allelic exclusion prevents expression of other Ig loci 1) Accessibility hypothesis txn of unrearranged gene stimulates rearrangement txn access affects whether rearrangement occurs 2) Heavy chain regulation block apoptosis and allow proliferation Stop VDJ rearrangement Start VJ κ rearrangement Pro-B to Pre-B also has loss of CD43 marker 3) Pre-B cell receptor complex VpreB and λ5 are surrogate light chains, help heavy chains fold Required to progress to Pre-B cell, otherwise apoptosis C. Two types of B cells
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