INTRACELLULAR SIGNALING FOR INDUCIBLE ANTIGEN RECEPTOR-MEDIATED FAS RESISTANCE IN B-CELLS

CD40 ligand-activated B cells are sensitive targets for CD4(+) Th1 eff ector cells that kill in a Fas-dependent fashion. Susceptibility to ap optosis is counteracted by Ag receptor binding that produces a state o f resistance to Fas engagement in otherwise sensitive targets. In the present study, protection from Th1-mediated apoptosis was found to be induced by protein kinase C and calcium signals, which in combination mimicked the level of Fas resistance produced by surface Ig engagement . Signaling for Fas resistance did not alter Fas expression. Furthermo re, B cells that were protected against Th1-mediated apoptosis were al so resistant to apoptosis mediated by soluble, rFas ligand. Taken toge ther, these results indicate that signaling for protection against Fas -mediated apoptosis does not depend on alteration of the interaction b etween B cell target and Th1 effector populations. Instead, surface Ig M-derived protein kinase C and calcium signals appear to produce an in tracellular change in the Fas signaling pathway that develops over a p eriod of hours and interferes with the apoptotic process through a mec hanism that depends on protein synthesis.