Antigenic specificities of human monoclonal and polyclonal IgM rheumatoid factors. The C gamma 2-C gamma 3 interface region contains the major determinants.
The binding site specificity of 12 monoclonal and 11 polyclonal IgM rheumatoid factors (RF) isolated from human plasma or serum has been studied. All IgM RF bound best to sites on IgG and intact Fc. The monoclonal IgM RF did not bind at all to fragments lacking the C gamma 2 or C gamma 3 domains. In contrast, low level binding to the pFc' fragment, composed of the C gamma 3 domain, was seen with seven IgM RF, mainly from patients with rheumatoid arthritis (RA). IgG1 binding appeared to be a requisite specificity of all human IgM RF. IgM RF binding to IgG3 subclass was common among the monoclonal IgM RF. Most RA polyclonal IgM RF but only 2 of the monoclonal IgM RF possessed the IgG1, 2 and 4 binding pattern. Monoclonal IgM RF which bound best to histidine-modified IgG also bound well to IgG3. The 7-kDa fragment D of staphylococcal protein A inhibited the IgG binding of most monoclonal and to a lesser degree polyclonal IgM RF. Thus, the results indicate that the C gamma 2-C gamma 3 interface region of IgG contains the predominant determinants for monoclonal and polyclonal IgM RF. For some monoclonal IgM RF the binding site, even though at the interface of the C gamma 2 and C gamma 3 domains, is not the staphylococcal protein A site. Furthermore, polyclonal IgM RF possess specificities not encountered among the monoclonal IgM RF. These specificities may have special
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology; D000918:Antibody Specificity; D000939:Epitopes; D006801:Humans; D007127:Immunoglobulin Constant Regions / Q000276:immunology*; D007128:Immunoglobulin Fragments / Q000276:immunology; D007143:Immunoglobulin Heavy Chains / Q000276:immunology*; D007075:Immunoglobulin M / Q000276:immunology*; D007142:Immunoglobulin gamma-Chains / Q000276:immunology*; D011817:Rabbits; D012217:Rheumatoid Factor / Q000276:immunology*; D013205:Staphylococcal Protein A / Q000378:metabolism
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D000939:Epitopes; D007127:Immunoglobulin Constant Regions; D007128:Immunoglobulin Fragments; D007143:Immunoglobulin Heavy Chains; D007075:Immunoglobulin M; D007142:Immunoglobulin gamma-Chains; D013205:Staphylococcal Protein A; D012217:Rheumatoid Factor