Differential effect of anti-B7-1 and anti-M150 antibodies in restricting the delivery of costimulatory signals from B cells and macrophages.
B7-1 and M150 are potent costimulatory molecules expressed on B cells and macrophages. We have examined the capacity of Abs against B7-1 and M150 in differentially inhibiting the costimulatory signals delivered by macrophages and B cells to OVA-specific CD4+ T cells. The anti-B7-1 Ab significantly blocked the proliferation of Th cells, MLR, T cell help to B cells, and secretion of IFN-gamma when B cells were used to provide costimulation, but not when macrophages were used. In contrast, anti-M150 Ab significantly decreased the proliferation of Th cells, MLR, and production of IFN-gamma, when macrophages were utilized to provide costimulatory signals, but not when B cells were used as APC. However, when macrophages activated with IFN-gamma were used as a source of costimulation, like anti-M150 Ab, Ab to B7-1 also down-regulated the activation of Th cells. The significance of this finding is that M150 is a potent first costimulatory signal for initiating proliferation and secretion of IFN-gamma and providing cognate help for B cells by Th cells when the macrophage is used as an accessory cell. M150-induced IFN-gamma production induces the expression of B7-1 on the surface of macrophages, which then delivers a second cosignal for Th cells. B7-1 works efficiently when B cell provides cosignal. Both of the molecules promote Th1 activity, as evidenced by the inhibition of the secretion of IFN-gamma but not IL-4 by Th cells with anti-M150 and B7-1 Abs.
Agrewala
J N
JN
Institute of Microbial Technology, Chandigarh, India.
Suvas
S
S
Verma
R K
RK
Mishra
G C
GC
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism / Q000494:pharmacology*; D000937:Antigen-Antibody Reactions; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D018122:B7-1 Antigen / Q000096:biosynthesis / Q000276:immunology*; D001667:Binding, Competitive / Q000276:immunology; D015153:Blotting, Western; D005260:Female; D006801:Humans; D007106:Immune Sera / Q000494:pharmacology; D007074:Immunoglobulin G / Q000378:metabolism; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000378:metabolism; D018664:Interleukin-12 / Q000276:immunology; D007519:Isoantigens / Q000502:physiology; D008213:Lymphocyte Activation / Q000276:immunology*; D007959:Lymphocyte Culture Test, Mixed; D008264:Macrophages / Q000276:immunology / Q000378:metabolism*; D008285:Major Histocompatibility Complex / Q000235:genetics / Q000502:physiology; D008565:Membrane Proteins / Q000096:biosynthesis / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D015398:Signal Transduction / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000378:metabolism
D000911:Antibodies, Monoclonal; D018122:B7-1 Antigen; D007106:Immune Sera; D007074:Immunoglobulin G; D007519:Isoantigens; D008565:Membrane Proteins; D018664:Interleukin-12; D007371:Interferon-gamma