TRANSGENE EXPRESSION OF BCL-X(L) PERMITS ANTIIMMUNOGLOBULIN (IG)-INDUCED PROLIFERATION IN XID B-CELLS

Mutations in the tyrosine kinase, Btk, result in a mild immunodeficien cy in mice (xid). While B lymphocytes from xid mice do not proliferate to anti-immunoglobulin (Ig), we show here induction of the complete c omplement of cell cycle regulatory molecules, though the level of indu ction is about half that detected in normal B cells. Cell cycle analys is reveals that anti-Ig stimulated xid B cells enter S phase, but fail to complete the cell cycle, exhibiting a high rate of apoptosis. This correlated with a decreased ability to induce the anti-apoptosis regu latory protein, Bcl-x(L). Ectopic expression of Bcl-x(L) in xid B cell s permitted anti-Ig induced cell cycle progression demonstrating dual requirements for induction of anti-apoptotic proteins plus cell cycle regulatory proteins during antigen receptor mediated proliferation. Fu rthermore, our results link one of the immunodeficient trains caused b y mutant Btk with the failure to properly regulate Bcl-x(L).