SOLUBLE-ANTIGEN CAN CAUSE ENHANCED APOPTOSIS OF GERMINAL-CENTER B-CELLS

GERMINAL centres are dynamic microenvironments of B-lymphocyte differe ntiation, which develop in secondary lymphoid tissues during immune re sponses(1-3). Within germinal centres, activated B lymphocytes prolife rate and point mutations are rapidly introduced into the genes encodin g their immunoglobulin receptor(4-10). As a result, new specificities of B cells are created, including those with a heightened capacity to bind the immunizing antigen(4-11). Immunoglobulin gene mutation can al so lead to reactivity to self antigens(12-14). It has been suggested t hat any newly formed self-reactive B cells are eliminated within the g erminal centre in order to avoid autoimmunity(15,16). Here we present evidence that antigen-specific, high-affinity, germinal-centre B cells are rapidly killed by apoptosis in sits when they encounter soluble a ntigen. The effect seems to act directly on the B cells, rather than t hrough helper T cells. Furthermore, the apoptosis is unique to germina l-centre cells, and is only incompletely impeded by constitutive expre ssion of the proto-oncogene bcl-2. This phenomenon may reflect clonal deletion of self-reactive B cells within germinal centres.