IL-4 INDUCES FAS RESISTANCE IN B-CELLS

Activated B cells express Fas (CD95) and are targets for apoptosis ind uced by CD4(+) Th1 effector cells that kill in a Fas dependent fashion , We report here that IL-4 reverses the susceptibility to Fas-mediated apoptosis that characterizes CD40-stimulated primary B cells, IL-4-in duced Fas resistance is not associated with an alteration in the eleva ted level of Fas expression produced by CD40 ligand and does not depen d on additional receptor-mediated signals, However, IL-4-induced resis tance to Th1 cell-mediated cytotoxicity (Th1-CMC) develops more slowly than resistance mediated by surface Ig and is not affected by protein kinase C depletion, unlike anti-lg-induced Fas resistance, By these t wo criteria, IL-4- and anti-lg-induced resistance to Th1-CMC appear to be driven through distinct mechanisms; in keeping with this, suboptim al doses of IL-4 and anti-lg act in synergy to induce marked protectio n against Th1-CMC. An important role for IL-4-induced Fas resistance i s suggested by the observation that sera from IL-4-overexpressing tran sgenic mice contain autoreactive Abs.