T-B CELL-INTERACTION INHIBITS SPONTANEOUS APOPTOSIS OF MATURE LYMPHOCYTES IN BCL-2-DEFICIENT MICE

Bcl-2 expression is tightly regulated during lymphocyte development. M ature lymphocytes in Bcl-2-deficient mice show accelerated spontaneous apoptosis in vivo and in vitro. Stimulation of Bcl-2-deficient lympho cytes by anti-CD3 antibody inhibited the spontaneous apoptosis not onl y in T cells but also in B cells. The rescue of B cells was dependent on the presence of T cells, mainly through CD40L and interleukin (IL)- 4. Furthermore, we generated Bcl-2-deficient mice transgenic for a T c ell receptor or an immunoglobulin, both specific for chicken ovalbumin , to test for antigen-specific T-B cell interaction in the inhibition of the spontaneous apoptosis. The initial T cell activation by antigen ic peptides presented by B cells suppressed apoptosis in T cells. Subs equently, T cells expressed CD40L and released ILs, leading to the pro tection of B cells from spontaneous apoptosis. These results suggest t hat the antiapoptotic signaling via CD40 or IL-4 may be largely indepe ndent of Bcl-2. Engagement of the Ig alone was not sufficient for the inhibition of B cell apoptosis. Thus, the physiological role of Bcl-2 in mature lymphocytes may be to protect cells from spontaneous apoptos is and to extend their lifespans to increase the opportunity for T cel ls and B cells to interact with each other and specific antigens in se condary lymphoid tissues. Bcl-2, however, appears to be dispensable fo r survival once mature lymphocytes are activated by antigen-specific T -B cell collaboration.