Rheumatoid factor and immune networks.

Rheumatoid factors represent a normal component of the immune network. The autoantibodies promote complement fixation and clearance of immune complexes. They amplify the avidity of polyclonally induced IgG. Genes related to the primary structure of rheumatoid-factor light chains are widely distributed in the human population and have been conserved during the evolution and dispersion of the species. Products of these genes may be detected with anti-idiotypic antibodies against synthetic peptides corresponding to individual hypervariable regions on rheumatoid-factor light chains. Such anti-peptide antibodies provide unique reagents for analyzing the genetics of immunoglobulins in outbred populations. Precursors of rheumatoid factor are abundant among immature B lymphocytes. Some of these cells may tend to localize to mucosal surfaces, where they are stimulated directly by pathogenic microorganisms with polyclonal B cell-activating properties. Synthesis of rheumatoid factor regularly accompanies all secondary immune responses but is usually transient. Production of the autoantibody is T-cell dependent. The T cells may recognize antigen in an IgG-antigen immune complex that is processed and presented by B-cell precursors of rheumatoid factor. Rheumatoid factor-associated light-chain idiotypes are rare in serum IgG and on IgG myeloma proteins. They are common among monoclonal IgM proteins and on the surface of the malignant B cells from patients with chronic lymphatic leukemia. The rheumatoid factors that are produced by patients with mixed cryoglobulinemia, or primary Sjogren's syndrome can share idiotypic antigens with monoclonal rheumatoid factors. Rheumatoid factor synthesis in the diseases may reflect an abnormal proliferation of B-cells that is not antigen-driven and that can degenerate into malignancy. The rheumatoid factors in patients with rheumatoid arthritis are diverse and almost certainly represent the outcome of antigen-induced, T cell-dependent mechanisms. The antigens that drive the T cells have not been identified but could represent exogenous microorganisms, self components, or idiotypic antigens that fortuitously interact with rheumatoid factors.