BCL-X EXHIBITS REGULATED EXPRESSION DURING B-CELL DEVELOPMENT AND ACTIVATION AND MODULATES LYMPHOCYTE SURVIVAL IN TRANSGENIC MICE

We have assessed during B cell development, the regulation and functio n of bcl-x, a member of the bcl-2 family of apoptosis regulatory genes . Here we show that Bcl-x(L), a product of bcl-x, is expressed in pre- B cells but downregulated at the immature and mature stages of B cell development. Bcl-x(L) but not Bcl-2 is rapidly induced in peripheral B cells upon surface immunoglobulin M (IgM) cross-linking, CD40 signali ng, or LPS stimulation. Transgenic mice that overexpressed Bcl-x(L) wi thin the B cell lineage exhibited marked accumulation of peripheral B cells in lymphoid organs and enhanced survival of developing and matur e B cells. B cell survival was further increased by simultaneous expre ssion of bcl-x(L) and bcl-2 transgenes. These studies demonstrate that Bcl-2 and Bcl-x(L) are regulated differentially during B cell develop ment and activation of mature B cells. Induction of Bcl-x(L) after sig naling through surface IgM and CD40 appears to provide mature B cells with an additional protective mechanism against apoptotic signals asso ciated with antigen-induced activation and proliferation.