ECTOPIC EXPRESSION OF BCL-2, BUT NOT BCL-X(L) RESCUES RAMOS B-CELLS FROM FAS-MEDIATED APOPTOSIS

The human Burkitt lymphoma Ramos B cell line can be induced to undergo apoptosis in response to a variety of different agents, including cal cium ionophores, anti-immunoglobulin (Ig) and macromolecular synthesis inhibitors. In addition, following up-regulation of the Fas (CD95) su rface receptor by CD40 ligation, these cells also become susceptible t o apoptosis induction by Fas ligation. We have previously shown that p rotection from calcium ionophore- and macromolecular synthesis inhibit or-induced apoptosis by CD40 ligation is associated with a rapid up-re gulation of Bcl-x(L), followed by a more moderate and delayed up-regul ation of Bcl-2. We show here that overexpression of Bcl-x(L), like Bcl -2, protects Ramos cells from apoptosis induction in response to calci um ionophore, anti-Ig and macromolecular synthesis inhibition. However , in contrast to Bcl-2, ectopic overexpression of Bd-x(L) does not res cue from Fas-mediated apoptosis. Thus, in Ramos B cells, the Fas apopt otic pathway exhibits differential sensitivity to inhibition by Bcl-2 family members. These findings also suggest that CD40 signaling provid es a switch which renders the cells susceptible to Fas-ligand mediated apoptosis through up-regulation of Fas whilst affording protection fr om anti-Ig-induced apoptosis through up-regulation of Bcl-x(L).