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COMPONENTS OF THE BCR

COMPONENTS OF THE BCR. Ig molecules do not have ITAMS. Ig a and Ig b have ITAMS. Ig molecules recognize antigen. Ig a and Ig b transduce signals. BCR CROSSLINKING INITIATES SIGNAL TRANSDUCTION. All isotypes of Ig initiate the same signal transduction cascade.

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COMPONENTS OF THE BCR

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  1. COMPONENTS OF THE BCR Ig molecules do not have ITAMS Iga and Igb have ITAMS Ig molecules recognize antigen Iga and Igb transduce signals

  2. BCR CROSSLINKING INITIATES SIGNAL TRANSDUCTION All isotypes of Ig initiate the same signal transduction cascade

  3. BCR CLUSTERING LEADS TO ITAM PHOSPHORYLATION The first step: activation of tyrosine kinases blk, lyn, fyn The second step: blk, fyn or lyn phophorylate ITAM on Igb The third step: Syk docks on Igb and sets off the cascade

  4. THE BCR SIGNALING CASCADE Clustering allows CD45 to activate blk, lyn, fyn Activated tyr kinases phosphorylate ITAMS Syc docks Signal cascade leads to gene transcription

  5. THE BCR CO-RECEPTOR Signaling is enhanced by other proteins that associate with BCR Three components to the Co-receptor: CD19, CD21 (CR2), CD81 CD19 is the signaling component BCR associated lyn phosphorylates CD19

  6. B CELL ACTIVATION REQUIRES TWO SIGNALS • Interaction with antigen initiates the antibody response • The second signal can be provided by an “armed” helper T cell • Some microbial antigens can provide both signal and are • T cell independent or TI antigens

  7. B CELL ACTIVATION DEPENDS ON CONCENTRATION OF TI ANTIGEN

  8. COMPARISON OF TD AND TI ANTIGENS

  9. TO PROVIDE HELP THE T CELL AND B CELL MUST RECOGNIZE THE SAME ANTIGEN The T cell and B cell recognize different parts of the same antigen T cells only recognize peptide (protein antigen)

  10. T AND B CELL RECOGNITION OF BACTERIA The association of protein with bacterial polysaccharide allows a TD response

  11. B CELLS AND T CELLS MEET IN LYMPH NODES

  12. T-B Contact: • T cells “face” B cell • Contact prevents IL-4 from • assisting irrelevant B cells

  13. T-B INTERACTION LEADS TO A PRIMARY FOCUS • B Cells can mature to plasma cells or • B cells can enter follicles and form a germinal center

  14. T CELL PRODUCTS STIMULATE B CELL PROLIFERATION AND DIFFERENTIATION • CD40L (T) with CD40 (B) • IL-4 causes B cell proliferation and isotype switching • IL-5 and IL-6 are involved in maturation and Ig secretion • CD30 (B) with CD30L (T) • BLyS and its receptor TACI on B Cells TNF/TNF receptor family

  15. B CELLS VS PLASMA CELLS

  16. B CELL MATURATION IS ASSOCIATED WITH CHANGES IN THE FORM OF EXPRESSED IMMUNOGLOBULIN M + ++++ +/- S - ++++ +++++++

  17. M1 1 2 3 s ALL CH GENES ARE ORGANIZED SIMILARLY M1 M2 1 2 3 4 s Cm 1 2 3 4 M2 M1 s Ce 1 2 3 M1 M2 s Cg2b Ca

  18. A. M1 1 2 3 s Ca sec AAAAAn mem AAAAAn B. M2 M1 1 2 3 4 s Cm sec AAAAAn mem AAAAAn MEMBRANE AND SECRETED FORMS OF Ig ARE GENERATED BY DIFFERENTIAL mRNA PROCESSING

  19. Some of the B cells from the primary focus initiate a germinal center

  20. GERMINAL CENTER

  21. CENTROBLASTS WITH HIGH AFFINITY BCR ARE RESCUED Survival signals can come from T cells or FDCs Most B cells die Surviving B cells can become plasma cells or memory cells

  22. T CELL DERIVED CYTOKINES DIRECT ISOTYPE SWITCHING

  23. VDJ Cm Cd Cg3 Cg1 Cg2b Cg2a Ce Ca Sm Sg3 Sg1 Sg2b Sg2a Se Sa Ig3 Ig1 Ig2b Ig2a Ie Ia TGF-b+ LPS VDJ Cm Cd Cg3 Cg1 Cg2b Cg2a Ce Ca Sm Sg3 Sg1 Sg2b Sg2a Se Sa Ig3 Ig1 Ig2b Ig2a Ie Ia Sm/Sa Ia Cm Cd Ce VDJ Ca + Sm/Sa Cg3 Cg2a Cg1 Cg2b STEPS IN ISOTYPE SWITCHING

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