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B-cell development & Activation B cell and T cell.

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Presentation on theme: "B-cell development & Activation B cell and T cell."— Presentation transcript:

1 B-cell development & Activation B cell and T cell

2 B-cell development Maturation ; antigen-independent Activation and Differentiation ; antigen-dependent

3 B-cell maturation

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6 mIgs at different stage of B-cell differentiation Roles of Pre-B-cell receptor ;

7 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

8 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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10 Light-chain editing ; escape negative selection

11 B-cell activation and Proliferation Thymus-dependent (TD) and thymus-independent (TI) Ag

12 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

13 Initiation of Signal transduction activated by BCR

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15 B-cell co-receptor complex

16 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

17 T-B conjugate Cytokines CD40L/CD40 interaction

18 Negative selection of mature B cells in the periphery Anergy

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21 The Humoral response ; primary vs. secondary response

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23 Carrier effect

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27 B-cell differentiation in GC, Affinity maturation and selection ; FDC Class switching Formation of effector B cells

28 Somatic hypermutation – affinity maturation

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31 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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