B-CELL ACTIVATION AND MATURATION
The enormous diversity of the normal B-cell-antibody repertoire initiates in the bone marrow where B-lymphocytes rearrange their immunoglobulin (Ig) variable (V) region gene segments coding for the B cell’s receptor for antigen (BCR). The diversity in the repertoire continuous to grow after binding antigen, when the B cells enter a lymphoid follicle and, with the help of other cells and cytokines, creates a structure called the germinal center (GC) where the cell proliferates and accumulates somatic mutations in its BCR-encoding genes. These mutations may produce amino acid changes in the binding site BCR, which can improve or create new antigen-binding specificity. Enhanced affinity B cells survive, whereas those having BCRs that either do not bind antigen or bind self-antigens die.The GC reaction usually occurs in secondary lymphoid follicles with the help of T lymphocytes. This mutation and selection process can take place in response to bacteria without T-cell help in the marginal zones outside of lymphoid follicles, although in this case, antigenic stimulation does not always induce mutation of IgVH genes.