Induction of IgG rheumatoid factor (RF) production by antibody-antibody (RF-like) immune complexes: the role of T cells, complement and Fc gamma receptors.
Rheumatoid factors (RF) are autoantibodies with specificity for the constant regions of IgG molecules. They are found in several immunopathological diseases. The mechanism(s) by which these autoantibodies are produced is largely unknown. We have previously shown that a single injection of RF-like immune complexes (ICs) into mice selectively induced an intense IgG1-antibody production with RF activity. This response was sustained for several months and did not resemble a conventional immune response to an antigen or other immune complexes. In the present study, we sought to elucidate the mechanism for the IgG1 RF response to RF-like ICs. Therefore, the roles of CD4+ T cells, complement and Fc gamma receptors were analysed. In order to characterize the role of CD4+ T cells, RF-like induced IgG1-RF production was analysed in NZB mice treated with a monoclonal antibody (mAb) against the CD4 molecule, which resulted in complete abrogation of IgG1 RF production. To evaluate the importance of Fc gamma Rs, the effect of RF-like ICs was tested in mice deficient for RF gamma RI/III. A significant decrease in the numbers of IgG1 antibody secreting cells, as well as in serum IgG1 RF levels, was found in the deficient mice, as compared with their normal outbred littermates. The role of complement in RF-like ICs mediated IgG1 RF was tested in complement depleted NZB mice, using Cobra venom factor. The IgG1 RF response in complement depleted and intact mice was comparable. Thus, our results demonstrate that RF-like immune complexes selectively induce an Fc gamma R-dependent, complement independent antibody response in mice.
Nordström
E
E
Department of Immunology, Arrhenius Laboratories for Natural Sciences, Stockholm University, Sweden.
Möller
E
E
Abedi-Valugerdi
M
M
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000008:administration & dosage / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000276:immunology; D000936:Antigen-Antibody Complex / Q000008:administration & dosage / Q000276:immunology*; D016175:B-Lymphocyte Subsets / Q000276:immunology; D015704:CD4 Antigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003165:Complement System Proteins / Q000276:immunology*; D004546:Elapid Venoms / Q000494:pharmacology; D005260:Female; D005434:Flow Cytometry; D007073:Immunoglobulin E / Q000096:biosynthesis / Q000097:blood / Q000235:genetics; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D007156:Immunologic Memory; D008211:Lymphocyte Cooperation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008814:Mice, Inbred NZB; D018345:Mice, Knockout; D017452:Receptors, IgG / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D012217:Rheumatoid Factor / Q000008:administration & dosage / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D013154:Spleen / Q000276:immunology
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D015704:CD4 Antigens; D004546:Elapid Venoms; D007074:Immunoglobulin G; D017452:Receptors, IgG; C016310:cobra venom factor; D007073:Immunoglobulin E; D003165:Complement System Proteins; D012217:Rheumatoid Factor