Ligation of HLA class II molecules promotes sensitivity to CD95 (Fas antigen, APO‐1)‐mediated apoptosis

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Abstract
CD95 (Fas antigen/APO‐1) is up‐regulated in activated lymphocytes, and monoclonal antibody (mAb) to CD95 induces apoptosis. HLA class II molecules play a key role in antigen presentation, ligation of which induces signal transduction. We examined 18 lymphoid cell lines (15 B cell and 3 T cell lines) to investigate the effects of ligation of HLA class 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 cell lines, two Burkitt lines were resistant to anti‐CD95 mAb in spite of high expression of CD95. In three of five non‐Burkitt B‐blastoid lines, CD95‐mediated apoptosis was augmented by treatment with anti‐HLA class II mAb, while the other two lines lacking CD95 were resistant to anti‐CD95 mAb. Three plasmacytic cell lines showed CD95‐mediated apoptosis, 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 class II antigen‐positive T cell lines, CD95‐mediated apoptosis was observed to some degree in one cell line but was not promoted by the treatment with anti‐HLA class II mAb, and the other two cell lines were resistant to anti‐CD95 mAb. Ligation of HLA class II molecules did not alter CD95 expression in the five cell lines examined, except Su‐DHL‐4 originated from a follicular lymphoma, which showed slight up‐regulation. Taken together, ligation of HLA class II molecules apparently promotes CD95‐mediated apoptosis in immature B cells and non‐Burkitt B blasts. These findings highlight the role of HLA class II molecules in CD95‐mediated apoptosis, which may facilitate rapid clearance of functionally useless cells from the immune system and might be involved in negative selection of B cells.