Autoimmune mice make anti-Fc gamma receptor antibodies.
We demonstrate, using a recombinant truncated Fc gamma RII molecule as a probe, the presence of anti-Fc gamma R antibodies in several strains of autoimmune mice. Affinity chromatography on a truncated Fc gamma R column of pooled sera from aged NZB females resulted in isolation of 16 micrograms of IgM per ml of serum, approximately 2% of the total IgM; no anti-Fc gamma R IgM was found in sera from C58/J mice. Mice with high titers of anti-Fc gamma R IgM also had anti-Fc gamma R IgG. Affinity-purified anti-Fc gamma R IgG bound to Fc gamma R-bearing cells. A good correlation was found between the presence of anti-Fc gamma R Ig and impaired phagocytosis of immune complexes in autoimmune strains such as NZB or NZB/NZW F1. Sera with high titers of anti-Fc gamma R Ig from NZB and motheaten mice inhibited the binding of soluble immune complexes. Furthermore, BXSB, a lupus-prone mouse strain that does not produce anti-Fc gamma R Ig, shows normal macrophage binding and phagocytosis of immune complexes. A set of four IgM mAbs that bind to Fc gamma R was identified. These antibodies were polyspecific; some were directed against DNA, and others recognized a wide variety of antigens including histones, thyroglobulin, and transferrin, but all anti-Fc gamma R IgM antibodies effectively inhibited the binding of IgG1 anti-DNP/DNP20BSA complexes to J774 macrophages. The role of anti-Fc gamma R Ig in autoimmunity remains to be established. It may act to crosslink and activate Fc gamma Rs on neutrophils, macrophages, NK, and mesangial cells, or it may desensitize Fc gamma R function of Fc gamma R-bearing cells.
Boros
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Department of Biochemistry, Mount Sinai School of Medicine, New York, New York 10029.
Chen
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JM
Bona
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Unkeless
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D000375:Aging; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000032:analysis*; D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex / Q000276:immunology; D000943:Antigens, Differentiation / Q000276:immunology*; D001327:Autoimmune Diseases / Q000276:immunology*; D002846:Chromatography, Affinity; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D007074:Immunoglobulin G / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D011961:Receptors, Fc / Q000276:immunology*; D017452:Receptors, IgG
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D000943:Antigens, Differentiation; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D011961:Receptors, Fc; D017452:Receptors, IgG