Fc receptors for mouse IgG1 on human monocytes: polymorphism and role in antibody-induced T cell proliferation.
In previous studies, it was shown that there is polymorphism in the mitogenic effect of mouse IgG1 monoclonal antibodies against the T3 antigen of human T cells. This polymorphism implies that IgG1 anti-T3 antibodies are not mitogenic for T cells from 30% of healthy individuals. The present results demonstrate that this polymorphism is caused by polymorphism of an Fc receptor for mouse IgG1, present on human monocytes. The Fc receptor for murine IgG1 could be detected by a newly developed rosetting assay on monocytes from all individuals responsive to the mitogenic effect of IgG1 anti-T3 antibodies. This Fc receptor was not detectable on monocytes from those individuals exhibiting no mitogenic responses to IgG1 anti-T3 monoclonal antibodies. Cross-linking of T3 antigens appears to be essential for antibody-induced mitosis of T cells, because mononuclear cells that did not proliferate in response to WT 31 (an IgG1 antibody against T3 antigen) showed a proliferative response to Sepharose beads coated with WT 31. The Fc receptor--if functionally present--may be involved in the cross-linking of T3 antigens through anti-T3 antibodies. Further evidence for the involvement of this Fc receptor in antibody-induced T cell proliferation was provided by inhibition studies. Immune complexes containing IgG1 antibodies were able to inhibit the proliferative response to IgG1 anti-T3 antibodies. This inhibition by immune complexes appears to be mediated through the monocyte Fc receptor for mouse IgG1. These findings are important for the interpretation of previously described inhibitory effects of anti-T cell monoclonal antibodies on T cell proliferation, and show that such inhibitory effects may be monocyte-mediated (via immune complexes) rather than caused by a direct involvement of the respective T cell antigens in T cell mitosis. The Fc receptor for mouse IgG1 plays a role in antibody-induced T cell proliferation. Its polymorphism may have important implications for the therapeutic use of IgG1 monoclonal antibodies.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000502:physiology*; D001666:Binding Sites, Antibody; D001667:Binding, Competitive; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D008934:Mitogens / Q000494:pharmacology; D009000:Monocytes / Q000378:metabolism*; D011110:Polymorphism, Genetic; D011961:Receptors, Fc / Q000235:genetics* / Q000276:immunology; D017452:Receptors, IgG; D012397:Rosette Formation; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D008934:Mitogens; D011961:Receptors, Fc; D017452:Receptors, IgG