Synovial IgG rheumatoid factors show evidence of an antigen-driven immune response and a shift in the V gene repertoire compared to IgM rheumatoid factors.
We have established IgG rheumatoid factor (RF)-secreting hybridoma cell lines from the synovial tissues of three patients from whom we have previously characterized several IgM RF. The IgG RF bind human and rabbit IgG and form intracellular complement-fixing complexes indicative of a self association process in vivo. Nucleotide sequence analysis revealed that two IgG RF used VHIII gene segments, while one used a VHI gene segment. The VL gene usage consisted of a V kappa 1, a V lambda 2 and a V kappa 4/V kappa 6 hybrid, confirming our previous findings that many different VL genes can contribute to RF specificity. Although the IgG RF used VH genes from the same families that dominated the IgM RF response, two of the actual gene segments employed were not found among the IgM RF. In contrast to IgM RF, which in general were not very mutated, the IgG RF showed somatic mutations characteristic of an antigen-driven immune response.
Institute of Immunology and Rheumatology, Oslo, Norway.
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I
Randen
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V
Pascual
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K
Victor
K M
KM
Thompson
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O
Førre
J D
JD
Capra
J B
JB
Natvig
D000595:Amino Acid Sequence; D000916:Antibody Diversity; D000941:Antigens; D001483:Base Sequence; D015322:Gene Rearrangement, B-Lymphocyte; D005803:Genes, Immunoglobulin; D006801:Humans; D006825:Hybridomas; D007074:Immunoglobulin G / Q000276:immunology*; D007075:Immunoglobulin M / Q000276:immunology*; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D012217:Rheumatoid Factor / Q000276:immunology*; D013582:Synovial Fluid / Q000276:immunology
D000941:Antigens; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007135:Immunoglobulin Variable Region; D012217:Rheumatoid Factor