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 2Progression signal ; drive from G1 into S

Initiation of Signal transduction activated by BCR

B-cell co-receptor complex

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

T-B conjugate

CytokinesCD40L/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