Differential effect of anti-B7-1 and anti-M150 antibodies in restricting the delivery of costimulatory signals from B cells and macrophages

Abstract

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.