PARTICIPATION OF THE BCL-2 AND FAS MOLECULES IN EXPERIMENTAL APOPTOSIS OF SPLEEN B-LYMPHOCYTES

Background. Homeostasis in the immune system is based on equilibrium b etween rates of cell renewal and cell death. Failure of elimination of undesirable autoreactive B cell clones may lead to autoimmune disorde rs. Objective. To assess the participation of the Ecl-2 and Fas molecu les in the regulation of B lymphocyte death. Methods. We used two stra ins of mice known to have deficient mechanisms of apoptosis, namely th e transgenic C57BL/6-E mu-bcl-2-22 expressing the bcl-2 transgene on B cells, and the C57BL/6-lpr/lpr mutant, lacking the expression of a fu nctional Fas molecule. Both strains develop a systemic lupus erythemat osus-like disease with serum autoantibodies and splenomegaly. We induc ed apoptosis by th ree different treatments: dexamethasone, gamma irra diation and hyperthermia. The proportion of cells in apoptosis was det ermined with the TUNEL method. Results. Radiation or hyperthermia indu ced apoptosis was inhibited more effectively by having the lpr mutatio n than the proto-oncogene bcl-2, but the latter conferred higher resis tance to apoptosis by dexamethasone. Conclusions. Our findings suggest that the role of molecules regulating cell death may relate to the st imuli used to induce apoptosis, and that both the lpr mutation and the overexpression of the proto-oncogene bcl-2 protect B cells from apopt osis induced by the three treatments tested.