bcl-2 transgene expression inhibits apoptosis in the germinal center and reveals differences in the selection of memory B cells and bone marrow antibody-forming cells

Immunization with T cell-dependent antigens generates long-lived memory B c ells and antibody-forming cells (AFCs). Both populations originate in germi nal centers and, predominantly, produce antibodies with high affinity for a ntigen. The means by which germinal center B cells are recruited into these populations remains unclear. We have examined affinity maturation of antig en-specific B cells in mice expressing the cell death inhibitor bcl-2 as a transgene. Such mice had reduced apoptosis in germinal centers and an exces sive number of memory B cells with a low frequency of V gene somatic mutati on, including those mutations encoding amino acid exchanges known to enhanc e affinity. Despite the frequency of AFCs being increased in bcl-2-transgen ic mice, the fraction secreting high-affinity antibody in the bone marrow a t day 42 remained unchanged compared with controls. The inability of BCL-2 to alter selection of bone marrow AFCs is consistent with these cells being selected within the germinal center on the basis of their affinity being a bove some threshold rather than their survival being due to a selective com petition for an antigen-based signal. Continuous competition for antigen do es, however, explain formation of the memory compartment.