title: Ligation of HLA class II molecules promotes sensitivity to CD95 (Fas antigen, APO-1)-mediated apoptosis.
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 I 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 call 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.
authors.affiliation: Department of Pathology, School of Medicine, Okayama University, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Yoshino
authors.forename: L
authors.initials: L
authors.lastname: Cao
authors.forename: R
authors.initials: R
authors.lastname: Nishiuchi
authors.forename: Y
authors.initials: Y
authors.lastname: Matsuo
authors.forename: I
authors.initials: I
authors.lastname: Yamadori
authors.forename: E
authors.initials: E
authors.lastname: Kondo
authors.forename: N
authors.initials: N
authors.lastname: Teramoto
authors.forename: K
authors.initials: K
authors.lastname: Hayashi
authors.forename: K
authors.initials: K
authors.lastname: Takahashi
authors.forename: N
authors.initials: N
authors.lastname: Kamikawaji
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism; D000954:Antigens, Surface / Q000096:biosynthesis / Q000502:physiology*; D017209:Apoptosis / Q000502:physiology*; D002460:Cell Line; D005434:Flow Cytometry; D006681:HLA-D Antigens / Q000276:immunology* / Q000378:metabolism*; D006682:HLA-DP Antigens / Q000276:immunology / Q000378:metabolism; D006683:HLA-DQ Antigens / Q000276:immunology / Q000378:metabolism; D006801:Humans; D019014:fas Receptor
chemical_list: D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D006681:HLA-D Antigens; D006682:HLA-DP Antigens; D006683:HLA-DQ Antigens; D019014:fas Receptor