INDUCTION OF SOMATIC MUTATION IN A HUMAN B-CELL LINE IN-VITRO

Both the B cell-surface trigger(s) and the intracellular molecular mec hanism(s) of somatic hypermutation in immunoglobulin (Ig) variable reg ion genes remain unknown, partly because of the lack of a simple and r eproducible in vitro model. Here, we show that upon surface immunoglob ulin cross-linking followed by coculture with activated cloned T cells , the Burkitt's lymphoma cell line BL2 is induced to mutate its IgV(H) gene. Repeated activation of BL2 cells increased the frequency of mut ation. The in vitro-induced mutations, which do not affect the IgM con stant region, are point mutations distributed over the entire V(H)DJ(H ) gene segment and do not show evidence of antigen-driven selection.