Selective induction of rheumatoid factors by superantigens and human helper T cells.
Production of autoantibodies specific for the Fc region of autologous IgG, called rheumatoid factors (RF), is a characteristic finding in patients with rheumatoid arthritis (RA). To study the requirements regulating the synthesis of these autoantibodies, we have cloned human helper T cells and co-cultured them with purified B cells. To mimic cognate T-B cell interaction, we have used bacterial superantigens that function by cross-linking HLA molecules on the B cell with selected T cell receptor (TCR) molecules expressing a particular polymorphism of the V beta gene segment. Data presented here demonstrate that the staphylococcal enterotoxin D (SE D), but not other bacterial superantigens, exhibits an ability to induce IgM, IgG, and especially RF production, in B cells from RA patients and normal individuals. Comparison with the polyclonal antibody production in B cell cultures driven by anti-CD3-stimulated T cell clones confirmed that SE D shifted the repertoire of secreted antibodies toward immunoglobulins with Fc binding specificity, suggesting that SE D preferentially stimulates RF+ B lymphocytes. B cells with the potential to secrete RF were highly frequent in RA patients, requiring as few as 150 peripheral B cells/culture to detect RF in the culture supernatants. SE D-induced RF synthesis was strictly dependent on the presence of selected CD4+T helper cells and required a direct membrane contact between B cells and T helper cells. Here, we propose a model that SE D selectively induces RF production depending on the availability of SE D responsive T cells in the TCR repertoire of the responder.
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Department of Medicine, Mayo Clinic and Foundation, Rochester, Minnesota 55905.
Goronzy
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Weyand
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D000942:Antigens, Bacterial / Q000276:immunology*; D015703:Antigens, CD / Q000032:analysis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000276:immunology; D001402:B-Lymphocytes / Q000502:physiology; D017252:CD3 Complex; D018956:CD5 Antigens; D004768:Enterotoxins / Q000276:immunology*; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D008213:Lymphocyte Activation; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000502:physiology; D012217:Rheumatoid Factor / Q000096:biosynthesis*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D000942:Antigens, Bacterial; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D018956:CD5 Antigens; D004768:Enterotoxins; D006684:HLA-DR Antigens; D011948:Receptors, Antigen, T-Cell; C019368:enterotoxin D, Staphylococcal; D012217:Rheumatoid Factor