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 ;

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

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

Light-chain editing ; escape negative selection

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

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

Initiation of Signal transduction activated by BCR

B-cell co-receptor complex

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

T-B conjugate Cytokines CD40L/CD40 interaction

Negative selection of mature B cells in the periphery Anergy

The Humoral response ; primary vs. secondary response

Carrier effect

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

Somatic hypermutation – affinity maturation

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