LIGATION OF HLA CLASS-II MOLECULES PROMOTES SENSITIVITY TO CD95 (FAS ANTIGEN, APO-1)-MEDIATED APOPTOSIS

CD95 (Fas antigen/APO-1) is up-regulated in activated lymphocytes, and monoclonal antibody (mAb) to CD95 induces apoptosis. HLA class II mol ecules play a key role in antigen presentation, ligation of which indu ces signal transduction. We examined 18 lymphoid cell lines (15 B cell and 3 T cell lines) to investigate the effects of ligation of HLA cla ss II molecules on CD95-mediated apoptosis. All of the five immature B cell lines were sensitive to anti-CD95 mAb, and ligation of HLA class II molecules promoted CD95-mediated apoptosis. In seven B-blastoid ce ll lines, two Burkitt lines were resistant to anti-CD95 mAb in spite o f high expression of CD95. In three of five non-Burkitt B-blastoid lin es, CD95-mediated apoptosis was augmented by treatment with anti-HLA c lass II mAb, while the other two lines lacking CD95 were resistant to anti-CD95 mAb. Three plasmacytic cell lines showed CD95-mediated apopt osis, but enhancement by anti-HLA class II mAb was slight in one cell line and was not observed in the other two lines. Out of three HLA cla ss II antigen-positive T cell lines, CD95-mediated apoptosis was obser ved to some degree in one cell line but was not promoted by the treatm ent with anti-KLA class II mAb, and the other two cell lines were resi stant to anti-CD95 mAb. Ligation of HLA class II molecules did not alt er CD95 expression in the five cell lines examined, except Su-DHL-4 or iginated from a follicular lymphoma, which showed slight up-regulation . Taken together, ligation of HLA class II molecules apparently promot es CD95-mediated apoptosis in immature B cells and non-Burkitt a blast s. These findings highlight the role of HLA class LI molecules in CD95 -mediated apoptosis, which may facilitate rapid clearance of functiona lly useless cells from the: immune system and might be involved in neg ative selection of B cells.