浙江大学医学免疫学经典课件免疫9、13B细胞.pptVIP

* * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * Antigen-activated B cells differentiate into centroblasts that undergo clonal expansion in the dark zone of the germinal centre. During proliferation, the process of somatic hypermutation (SHM) introduces base-pair changes into the V(D)J region of the rearranged genes encoding the immunoglobulin variable region (IgV) of the heavy chain and light chain; some of these base-pair mutations lead to a change in the amino-acid sequence. Centroblasts then differentiate into centrocytes and move to the light zone, where the modified antigen receptor, with help from immune helper cells including T cells and follicular dendritic cells (FDCs), is selected for improved binding to the immunizing antigen. Newly generated centrocytes that produce an unfavourable antibody undergo apoptosis and are removed. A subset of centrocytes undergoes immunoglobulin class-switch recombination (CSR). Cycling of centroblasts and centrocytes between dark and light zones seems to be mediated by a chemokine gradient, presumably established by stromal cells in the respective zones (not shown)14. Antigen-selected centrocytes eventually differentiate into memory B cells or plasma cells. * d. Th cells stimulate B cells to produce Abs of different heavy chain classes (isotypes) Heavy chain class switching is initiated by CD40L-mediated signals, and switching to different classes is stimulated by different cytokines. Ig heavy chain class (isotype) switching （蠕虫） Ig heavy chain class (isotype) switching Mechanisms of Ig heavy chain class switching e. Affinity maturation in Ab responses Affinity maturation is the process by which the affinity of Abs produced in response to a protein Ag increases with prolonged and repeated exposure to that Ag. The increase in affinity is due to point mutations in the V regions, and particularly in the Ag-binding HVR, of the Abs produced. Affinity maturation occurs in the germinal centers of lymphoid fol