B-cell tolerance to the B-cell receptor variable regions

An enormous number of B cells with different B-cell receptors (BCRs) are continuously produced in the bone marrow. BCRs are further diversified during the germinal center reaction. Due to extensive recirculation, B cells with mutually binding BCR are likely to meet in lymphoid organs. We have addressed possible outcomes of such an encounter in vitro. Blymphoma cells were transfected with complementary BCR, one transfectant expressing an Idiotype(+) (Id(+)) BCR and the other an anti-Id BCR. To exclude confounding effects of secreted Ig, the transfected B lymphoma cells only expressed membrane IgD. Coincubation of paired Id(+)/anti-Id lymphoma cells results in conjugate formation, signaling, activation of Caspase 3/7, and apoptosis of at least one of the two cells in the pair. Our data provide suggestive evidence for a mechanism whereby the B-cell compartment is partly purged of B cells with complementary BCRs.