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B-cell development & Activation

B-cell development & Activation. B cell and T cell. B-cell development. Maturation ; antigen-independent Activation and Differentiation ; antigen-dependent. B-cell maturation. mIgs at different stage of B-cell differentiation. Roles of Pre-B-cell receptor ;.

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B-cell development & Activation

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  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

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

  5. Molecules that are related to the B-c ell development • Transcription factors • E2A, EBF ; regulation of RAG-1 and l5 expression • BSAP (Pax-5) ; Vpre-B, l5, Ig heavy chain • Sox-4 • Surface Markers ; stage specific • Pro-B cell ; CD45R (B220), Ig-a/Ig-b, CD19, HSA(CD24), CD43, c-Kit, IL7R • Pre- B cell ; Pre-BCR, CD25 • Immature B cell ; mIgM

  6. Clonal deletion (negative selection) 90% of B-cells that express auto-antibodies against self-antigens are eliminated in the bone marrow

  7. Light-chain editing ; escape negative selection

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

  9. 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

  10. Initiation of Signal transduction activated by BCR

  11. B-cell co-receptor complex

  12. B-cell activation by TH Ag binging to mIg ; signal 1 Receptor-mediated endocytosis - Ag presentation /MHC II - B7 expression Activation of TH cell - B7-CD28 - Expression of CD40L B cell activation - CD40/CD40L ; signal 2 - Express cytokine receptors - Proliferation

  13. T-B conjugate Cytokines CD40L/CD40 interaction

  14. Negative selection of mature B cells in the periphery Anergy

  15. The Humoral response ; primary vs. secondary response

  16. Carrier effect

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

  18. Somatic hypermutation – affinity maturation

  19. 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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