Antibodies to HLA class I alpha1 domain trigger apoptosis of CD40-activated human B lymphocytes.
We analyzed herein whether antibodies to HLA class I alpha1 domain, which trigger apoptosis of activated T cells, may also control the growth/survival of human B lymphocytes. Addition of monoclonal antibody (MoAb) 90 (mouse IgG1) or YTH862 (rat IgG2b) was found to strongly inhibit the proliferation of CD40-activated total tonsil B cells as well as that of purified naive, germinal center, and memory B-cell subsets. This inhibitory effect was not prevented by addition of B-cell tropic factors, such as interleukin-2 (IL-2), IL-4, and IL-10, and was a result of induced B-cell apoptosis as shown by using a TUNEL assay and DNA electrophoresis. In contrast, engagement of another epitope of the alpha1 domain, as well as that of the alpha2 and alpha3 domains by specific anti-HLA class I MoAbs, failed to inhibit DNA synthesis and to induce apoptosis of CD40-activated B cells. As recently reported for acquisition of sensitivity to Fas (APO-1/CD95) -dependent apoptosis, susceptibility 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 together, these results show that engagement of the alpha1 domain of HLA class I induces apoptotic cell death of CD40-activated, but not of antigen-activated B cells, and would, therefore, suggest a possible role for HLA class I molecules in the control of B-cell homeostasis.
Genestier
L
L
Laboratory of Immunology, INSERM U80 UCBL, Hôpital E. Herriot, Lyon, France.
Meffre
G
G
Garrone
P
P
Pin
J J
JJ
Liu
Y J
YJ
Banchereau
J
J
Revillard
J P
JP
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology*; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000502:physiology; D019013:CD40 Antigens / Q000502:physiology*; D002478:Cells, Cultured; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G; D007739:L Cells; D008213:Lymphocyte Activation; D051379:Mice; D014066:Palatine Tonsil / Q000276:immunology; D051381:Rats; D014162:Transfection; D019014:fas Receptor / Q000096:biosynthesis
D000911:Antibodies, Monoclonal; D019013:CD40 Antigens; D015395:Histocompatibility Antigens Class I; D007074:Immunoglobulin G; D019014:fas Receptor