Signaling through MHC class II molecules blocks CD95-induced apoptosis

B cells are induced to express CD95 upon interaction with T cells. This int eraction renders the B cells sensitive to CD95-mediated apoptosis, but liga tion of proviability surface receptors is able to inhibit apoptosis inducti on. MHC class II is a key molecule required for Ag presentation to Th cells , productive T cell-B cell interaction, and B cell activation. We demonstra te here for the first time that MHC class II ligation also confers a rapid resistance to CD95-induced apoptosis, an affect that does not require de no vo protein synthesis. Signaling through class II molecules blocks the activ ation of caspase 8, but does not affect the association of CD95 and Fas-ass ociated death domain-containing protein. MHC class II ligation thus blocks proximal signaling events in the CD95-mediated apoptotic pathway.