ANTIBODIES TO HLA CLASS-I ALPHA-1 DOMAIN TRIGGER APOPTOSIS OF CD40-ACTIVATED HUMAN B-LYMPHOCYTES

We analyzed herein whether antibodies to HLA class I alpha 1 domain, w hich trigger apoptosis of activated T cells, may also control the grow th/survival of human B lymphocytes. Addition of monoclonal antibody (M oAb) 90 (mouse IgG1) or YTH862 (rat IgG2b) was found to strongly inhib it the proliferation of CD40-activated total tonsil B cells as well as that of purified naive, germinal center, and memory B-cell subsets. T his inhibitory effect was not prevented by addition of B-cell tropic f actors, such as interleukin-2 (IL-2), IL-4, and IL-10, and was a resul t of induced B-cell apoptosis as shown by using a TUNEL assay and DNA electrophoresis. In contrast, engagement of another epitope of the alp ha 1 domain, as well as that of the alpha 2 and alpha 3 domains by spe cific anti-HLA class I MoAbs, failed to inhibit DNA synthesis and to i nduce apoptosis of CD40-activated B cells. As recently reported for ac quisition of sensitivity to Fas (APO-1/CD95)-dependent apoptosis, susc eptibility to MoAb90- and YTH862-induced death was restricted to CD40- activated B cells, because resting and anti-IgM-activated B cells did not undergo apoptosis after HLA class I engagement, Moreover, ligation of the B-cell receptor protected CD40-activated B cells from both HLA class I- and Fas-mediated growth inhibition and apoptosis. Taken toge ther, these results show that engagement of the alpha 1 domain of HLA class I induces apoptotic cell death of CD40-activated, but not of ant igen-activated B cells, and would, therefore, suggest a possible role for HLA class I molecules in the control of B-cell homeostasis. (C) 19 97 by The American Society of Hematology.