The physiology of germinal centers.

GCs contain Ag-induced rapidly proliferating B cell blasts called centroblasts and centrocytes and are located in primary follicles of peripheral lymphoid tissue. Their peak development is at 7 to 10 d after Ag. The generation of memory B cells occurs in GCs, accompanied by frequent Ig isotype switching, Ig gene V region somatic hypermutation, and/or (in rabbits) gene conversion. The nature and function of the cell types that make up the microenvironment of the GC B cells, the CD4+ T cells and FDCs, are discussed in detail. The high rate of apoptosis that occurs in GCs is thought to be the result of processes of positive and negative selection ongoing in different compartments of GCs. The rescue of cells through high-affinity interaction with Ag localized on FDCs and subsequent presentation of Ag by GC B cells to T cells may represent the positive selection with apoptosis as the default pathway. Negative selection may occur, aimed at the prevention of autoimmunity caused by cells with mutated sIg binding to autoAgs. Some aspects of GC-derived lymphomas in humans and mice are also reviewed.