B-cell activation versus tolerance--the central role of immunoglobulin receptor engagement and T-cell help.

The critical variables responsible for the decision between activation and tolerance in the B-cell compartment were studied in the well-characterised hen egg lysozyme:antilysozyme transgenic model. Mature B-cells exposed to a low antigenic signal, which resulted in a receptor occupancy of between 5% and 25%, remained 'indifferent' (i.e. were neither activated nor tolerant), had a normal lifespan and recirculated through B-cell follicles. When receptor occupancy reached a critical threshold of approximately 50%, the B-cells became activated and moved to the outer T-cell zones where they died. This threshold appeared to be lower in the case of immature B-cells. On addition of T-cell help, however, the B-cells were rescued, proliferated and secreted antibody. Thus the outcome of the interaction between B-cells and antigen (self or foreign) is determined largely by the degree of antigen receptor engagement and availability of T-cell help.