Antigen receptor signalling in apoptosis-resistant mutants of WEHI 231 cells

Ligation of membrane immunoglobulin M (mIgM) induces cell cycle arrest and apoptosis in the WEHI 231 B-lymphoma cell line. The molecular mechanisms wh ich link receptor ligation and the nuclear events that underlie this respon se, have yet to be fully elucidated. Here we have examined the signals indu ced following mIgM cross-linking in variants of WEHI 231 that no longer und ergo apoptosis in response to this stimulus. Tyrosine phosphorylation of ce llular substrates in two of the variants is identical to that seen in wild- type cells but in one of the mutants, VS2.12, a restricted set of substrate s becomes tyrosine phosphorylated. In a second variant (E8), mIgM cross-lin king does not induce elevation of intracellular Ca2+, although tyrosine pho sphorylation of PLC gamma 2 is induced to an equivalent extent to that seen in WEHI 231 cells. A third variant, 2E10.F9, is resistant to apoptosis des pite the fact that all signals analysed appear to be similar to those induc ed in wild-type cells. Our findings show that resistance to apoptosis can a rise as a result of mutations affecting discrete stages of the mIgM signall ing pathway. The mutant lines reported here show defects that have not yet been identified in previous studies and are likely to be useful tools in di ssecting the signalling of cell death in B lymphocytes.