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Published byPatricia Simon Modified over 9 years ago
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B-cell development & Activation B cell and T cell
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B-cell development Maturation ; antigen-independent Activation and Differentiation ; antigen-dependent
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B-cell maturation
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mIgs at different stage of B-cell differentiation Roles of Pre-B-cell receptor ;
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Molecules that are related to the B-c ell development Transcription factors –E2A, EBF ; regulation of RAG-1 and 5 expression –BSAP (Pax-5) ; Vpre-B, 5, Ig heavy chain –Sox-4 Surface Markers ; stage specific –Pro-B cell ; CD45R (B220), Ig- /Ig- , CD19, HSA(CD24), CD43, c-Kit, IL7R –Pre- B cell ; Pre-BCR, CD25 –Immature B cell ; mIgM
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Clonal deletion (negative selection) 90% of B-cells that express auto-antibodies against self-antigens are eliminated in the bone marrow
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Light-chain editing ; escape negative selection
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B-cell activation and Proliferation Thymus-dependent (TD) and thymus-independent (TI) Ag
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Effective signals for B-cell activation Competence signal ; drive from G0 into G1, signal 1 and signal 2 Progression signal ; drive from G1 into S
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Initiation of Signal transduction activated by BCR
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B-cell co-receptor complex
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B-cell activation by T H Ag binging to mIg ; signal 1 Receptor-mediated endocytosis - Ag presentation /MHC II - B7 expression Activation of T H cell - B7-CD28 - Expression of CD40L B cell activation - CD40/CD40L ; signal 2 - Express cytokine receptors - Proliferation
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T-B conjugate Cytokines CD40L/CD40 interaction
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Negative selection of mature B cells in the periphery Anergy
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The Humoral response ; primary vs. secondary response
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Carrier effect
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B-cell differentiation in GC, Affinity maturation and selection ; FDC Class switching Formation of effector B cells
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Somatic hypermutation – affinity maturation
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Antibody-dependent cell-mediated cytotoxicity (ADCC) Membrane receptors for the Fc region of IgG –Specificity of the antibody directs non-specific cytotoxic cells to specific target cells –NK cells, macrophages, monocytes, neutrophils, eosinophils –Release of lytic enzymes at the site of Fc-mediated contact result in damage to the target cells –Tumor necrosis factor (TNF) –Perforin-mediated membrane damage
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