T-LYMPHOCYTE T-CELL B-CELL ACTIVATING MOLECULE CD40-L MOLECULES INDUCE NORMAL B-CELLS OR CHRONIC LYMPHOCYTIC-LEUKEMIA B-CELLS TO EXPRESS CD80 (B7 BB-1) AND ENHANCE THEIR COSTIMULATORY ACTIVITY/

Activation-induced cell surface molecules are involved in mediating bi directional T-B lymphocyte signaling that is important in the inductio n of T or B lymphocyte effector functions. In this regard, T-BAM/CD40- L is an activation-induced CD4(+) T cell surface molecule known to be important in inducing B cell effector functions. This report demonstra tes that T-BAM/CD40-L molecules on a Jurkat T cell leukemia subclone ( D1.1) or nonlymphoid 293 kidney cell transfectants induce B cells or B -CLL cells to express CD80 (B7/BB-1) in a manner that is specifically inhibited by anti-T-BAM/CD4O-L mAb 5C8. Because activation-induced B c ell surface molecules, such as CD80, deliver costimulatory signals to T cells that augment T cell proliferation, the functional costimulator y capacity of T-BAM/CD4O-L-primed B cells and B-CLL cells was studied. T-BAM/CD40-L-primed B cells or B-CLL cells augment the proliferative responses of allogenic T cells. Furthermore, T-BAM/CD40-L priming is s pecifically inhibited by mAb 5C8. Together, these studies demonstrate that T-BAM/CD40-L induces CD80 expression on resting B cells or B-CLL cells. Moreover, T-BAM/CD40-L signaling enhances B cell costimulatory capacity. These studies suggest that T-BAM/CD40-L molecules not only i nduce B cell differentiative processes that result in Ab secretion, bu t also enable B cells to prime Ag-specific T cells for subsequent clon al expansion.