Induction of Somatic Mutation in a Human B Cell Line In Vitro

Abstract Both the B cell–surface trigger(s) and the intracellular molecular mechanism(s) of somatic hypermutation in immunoglobulin (Ig) variable region genes remain unknown, partly because of the lack of a simple and reproducible in vitro model. Here, we show that upon surface immunoglobulin 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 mutation. The in vitro–induced mutations, which do not affect the IgM constant region, are point mutations distributed over the entire V H DJ H gene segment and do not show evidence of antigen-driven selection.