Fc gamma receptor-mediated suppression of gamma-interferon-induced Ia antigen expression on a murine macrophage-like cell line (P338D1).

Abstract

A variant (HS-1) of a murine macrophage cell line (P388D1) was obtained by cell cluster technique based on the Ia antigen expression induced by lymphokines. Receptors for both IgG2a and IgG2b but no detectable I-Ad are expressed on the surface of the majority of HS-1 cells. Exposure of HS-1 cell to concanavalin A supernatant or recombinant IFN-gamma resulted in the induction of I-Ad antigens on greater than 90% of the cells within 48 hr. The effects of lymphokines were transient and dependent on the synthesis of messenger RNA because the removal of lymphokines or the presence of actinomycin D both blocked Ia expression. The prior or simultaneous binding of monoclonal IgG2a or IgG2b antibodies complexed with sheep erythrocytes to respective cell surface Fc gamma R suppressed the Ia antigen inducing activity of lymphokines. Neither antibody nor antigen alone could suppress the effect of lymphokines. Inhibitors of phospholipase A2 or cyclooxygenase, which have been shown previously to suppress Fc gamma 2bR, but not Fc gamma 2aR, triggered activation of the adenylate cyclase system and reversed Fc gamma 2bR- but not Fc gamma 2aR-mediated suppression of IFN-gamma-induced Ia antigen expression.