Modulation of natural IgM binding and complement activation by natural IgG antibodies: a role for IgG anti-Gal alpha1-3Gal antibodies.
The most abundant natural IgG Abs in human serum are thought to be Abs specific for Gal alpha1-3Gal, a carbohydrate expressed in lower mammals. IgG Abs specific for Gal alpha1-3Gal have been postulated to contribute to host defense and to participate in the rejection of interspecies organ grafts. Our previous studies indicated, however, that IgM and not IgG anti-Gal alpha1-3Gal Abs activate complement on foreign surfaces, and thus the physiologic role of IgG anti-Gal alpha1-3Gal remains uncertain. We tested whether the IgG anti-Gal alpha1-3Gal in a human serum might in fact compete with IgM for binding and thus modulate complement fixation by IgM. Several lines of evidence suggested such competition might occur. First, the functional avidity of IgG and IgM for Gal alpha1-3Gal on cell surfaces were nearly within the same order of magnitude, and in some sera the molar concentrations of IgG and IgM anti-Gal alpha1-3Gal were comparable. Second, binding of human IgM to Gal alpha1-3Gal on cell surfaces was inversely correlated with the concentration of IgG anti-Gal alpha1-3Gal in serum. Third, combination of IgG and IgM Abs specific for Gal alpha1-3Gal demonstrated direct competition for binding. The presence of IgG anti-Gal alpha1-3Gal, which was predominantly IgG2, attenuated by up to 80% the fixation of C1q mediated by IgM, presumably by competing for antigenic sites recognized by IgM Abs that fix complement. Thus, IgG Abs specific for Gal alpha1-3Gal modulate complement activation by IgM specific for that structure and might in this way modulate the consequences that ensue when human blood is brought into contact with foreign organisms or xenogenic cells.
Yu
P B
PB
Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA.
Holzknecht
Z E
ZE
Bruno
D
D
Parker
W
W
Platt
J L
JL
D000818:Animals; D000918:Antibody Specificity; D015478:Antigens, Heterophile; D001667:Binding, Competitive; D002462:Cell Membrane / Q000276:immunology; D003167:Complement Activation; D004187:Disaccharides / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D007074:Immunoglobulin G / Q000097:blood / Q000145:classification / Q000378:metabolism*; D007075:Immunoglobulin M / Q000378:metabolism*; D066298:In Vitro Techniques; D008322:Mammals; D013045:Species Specificity
D015478:Antigens, Heterophile; D004187:Disaccharides; D007074:Immunoglobulin G; D007075:Immunoglobulin M; C055075:galactosyl-(1-3)galactose