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The Specificity of Synovial IgM Rheumatoid Factors (RF) for Genetically Engineered IgG Antibodies is not Affected by the Method used to Immortalize RF‐Producing B Cells
Author(s) -
Vincent R. Bonagura,
T Kwong,
Thomas P. Kenny,
Robbins Dl,
Morrison Sl
Publication year - 1999
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1046/j.1365-3083.1999.00475.x
Subject(s) - antibody , rheumatoid factor , genetically engineered , immunology , rheumatoid arthritis , immunoglobulin g , immunoglobulin m , chemistry , medicine , gene , biochemistry
Previously, we have shown that some rheumatoid factors (RFs) produced by Epstein–Barr virus (EBV)‐transformed B cells from patients with rheumatoid arthritis (EBV‐RA‐RF) appear to be disease‐specific autoantibodies that bind differently to defined epitopes on genetically engineered IgG antibodies, compared with RFs expressed by patients with Waldenström's macroglobulinaemia (Wmac‐RFs) and healthy immunized donors (HID‐RFs). To exclude the possibility that EBV transformation is responsible for these differences, we have now studied 15 other monoclonal IgM RFs from patients with RA that were produced by heterohybridoma–B‐cell fusion (HRA‐RFs). These HRA‐RFs show the same gross specificity profiles for IgG as do their EBV‐RA‐RF counterparts. However, when the specificities of the HRA‐RF and EBV‐RA‐RF panels were combined and compared with those RFs from patients with Wmac or HID, significant differences in binding specificity were again observed. Hybrid IgG3/4 antibodies made by exon shuffles between the IgG3 and IgG4 wild‐type genes, and families of IgG variant antibodies made by site‐directed mutagenesis, were used to map the fine specificity of HRA‐RFs. The fine specificity of HRA‐RFs were also similar to those of EBV‐RA‐RFs. These studies demonstrate that the method used for immortalizing IgM, RF‐producing B cells from RA patients does not influence the specificity of the RFs obtained. Furthermore, some RFs expressed in RA have distinct and unique specificities, and may therefore represent disease‐specific autoantibodies.