Chap 12

Kuby Immunology, Sixth Edition

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CHAPTER 12: CYTOKINES I. B-CELL MATURATION A. B Cell Development Three broad stages in production of plasma cells and memory B cells: 1) Maturation (Bone marrow): gene rearrangement of V(D)J for antigen specificity and negative selection 2) Activation (Periphery): mature cells proliferate in response to antigen, class switching Differentiation (Periphery): affinity maturation, somatic hypermutation, selection and production of effector (plasma cells) and memory cells Life of A B Cell in Primary and Secondary Lymphoid Organs
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CHAPTER 12: CYTOKINES Antigen-independent stage: only ~10% survive, small fraction of repertoire Antigen-dependent stage: days to weeks to encounter antigen or die Progenitor B cells proliferate in bone marrow Ig-gene rearrangement produces immature B cells Maturation Antigen-independent process Microenvironment in bone marrow – provided by stromal cells, which play two important roles 1) Interact directly with Pro-B and Pre-B cells 2) Secrete various cytokines that support the developmental process Some required bone marrow stromal cells: 1) Adhesion molecules: (1) VLA-4 (2) VCAM 2) Growth factor: (1) c-kit, (2) SCF ( S tem C ell F actor) 3) Cytokines: (1) IL-7 (IL-7 receptor) Heavy and light chain Ig Chain gene rearrangement Clonal deletion (negative selection → receptors to self-antigen leads to apoptosis) B Cell Microenvironment in Bone Marrow
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CHAPTER 12: CYTOKINES SCF S tem C ell F actor c-kit – tyrosine kinase B. Stages of B Cell Maturation Order of Maturation: Stem cell → Pro/Pre-B → immature B (IgM) → mature B (IgM and IgD) 1) Stem Cell 2) Progenitor B cell (Pro-B cell) Earliest distinctive B-lineage cell Expresses CD45R (a transmembrane tyrosine phosphatase) Ig-α/Ig-β of BCR + Heavy chain D → J recombination 3) Precursor B cell (Pre-B cell) Proliferation and differentiation of Pro-B to Pre-B requires microenvironment provided by bone marrow stromal cells Heavy chain V → DJ made + surrogate light chain proliferates 4) Immature B cell Still in bone marrow
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CHAPTER 12: CYTOKINES Light chain V → J made
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Chap 12 - CHAPTER 12 CYTOKINES I B-CELL MATURATION A B Cell...

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