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Monoclonal IgM rheumatoid factors generated from synovial B cells of rheumatoid arthritis patients react with beta 2-microglobulin. Monoclonal RF react with beta 2m.
Autoimmunity
June 1994
Department of Medicine, University of Florida, Gainesville 32610.
Four of 15 monoclonal human IgM rheumatoid factors (RF) derived from synovial B cells of patients with rheumatoid arthritis showed positive ELISA reactions with human beta 2-microglobulin. These findings were different from those previously noted using IgM RF derived from monoclonal Waldenstrom's paraproteins or the IgM components of mixed cryoglobulins, and resembled the anti-beta 2 microglobulin specificity of polyclonal IgM RF from patients with rheumatoid arthritis. Reactions of monoclonal IgM synovial RF with overlapping 7-mers of beta 2m sequence indicated major regions of positive reactivity at positions 57-64 and 89-95 which were maintained in the presence of high salt (300 mM NaCl) conditions.
View Article and Find Full Text PDFWe have determined the V region amino acid sequence and/or serologic markers (kIIIb, PSL2, and PSL3) of 24 IgM monoclonal autoantibodies with specificities of anti-gamma-globulin (RF), anti-I (cold agglutinin), anti-low density lipoprotein and anti-intermediate filaments. The data emphasize the overwhelming selection of the HumKv325/VkIIIb L chain for this family of autoantibodies. The few amino acid substitutions found within the VL regions were mainly concentrated in the complementarity-determining region 1.
View Article and Find Full Text PDFAs an alternative strategy to the use of proteolytic and chemical cleavage in the production of fragments of immunoglobulins retaining Fc effector functions, peptides representative of amino acid sequences constituting the putative active sites have been synthesized and assessed for biological activity in various in vitro systems. This approach has been adopted in attempts to define more precisely the autoantigenic epitope on human IgG against which anti-gamma-globulin antibodies (the so-called general 'rheumatoid factors'), found in the sera and joint fluids of patients with rheumatoid arthritis, are directed. Synthetic peptides representative of epsilon-chain sequences are being used in the production of antibodies (polyclonal and monoclonal) directed against specific epitopes within the Fc regions of human and rat IgE.
View Article and Find Full Text PDFThe complete amino acid sequence of five light chain variable (V) regions of human monoclonal IgM kappa rheumatoid factors (RF) was determined, and their cross-reactive idiotypes (CRI) were characterized with antibodies induced by immunization with synthetic peptides PSL2 and PSL3, corresponding to the second and third complementarity-determining regions (CDR) of the SIE light chain. Together with two additional RF studied previously, all seven RF belong to the V kappa IIIb sub-subgroup. The region encoded by the V kappa gene segment (positions 1 to 95) in all seven proteins was virtually identical in primary structure, whereas the sequence from positions 96 to 108 defined the usage of the J kappa 1 gene in three proteins and the J kappa 2 gene in four of them.
View Article and Find Full Text PDFA profound inability to produce IgG anti-2,4,6-trinitrophenyl (TNP) antibodies during the secondary immune response elicited by a T-dependent antigen was observed in aged MLR/lpr mice. This unresponsiveness is associated with a significantly low indirect anti-TNP plaque-forming cell response and a weak in vitro anti-TNP response upon the culture of keyhole limpet hemocyanin-primed T cells and TNP-primed B cells in the presence of TNP. The markedly low IgG anti-TNP response observed in aged MLR/lpr mice cannot be related to the presence of rheumatoid factors which are observed during the secondary response, since MRL +/+ and 129/J mice, (non-autoimmune disease strains), also produce significant amounts of anti-gamma-globulin antibodies yet mount a strong IgG anti-TNP response.
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