Transcript B-cell development & Acvivation

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 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
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 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
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