Monoclonal IgM, IgG, and IgA human rheumatoid factors produced by synovial tissue-derived, EBV-transformed B cell lines.
In an effort to study disease-related autoantibodies in rheumatoid arthritis (RA), rheumatoid factor (RF)-producing B cell lines were developed from the heterogeneous B cell populations infiltrating the synovial tissue of patients with arthritis. Over 125 EBV-transformed B cell cultures were derived from three patients: one with early pre-erosive RA, one with advanced RA, and one with osteoarthritis (OA). IgM, IgG, and IgA RF-producing B cell lines were found in all three series but with several significant differences. In each of the two RA patients, 22% of the Ig-producing cell lines secreted RF compared to 7% in the OA patient. The isotypes of these RF were mostly IgM in the early RA (62%) and the OA patient (60%) as contrasted to predominantly IgA (75%) and, to a lesser extent, IgG (12.5%) in the advanced RA patient. Analyses of the light (L) chain composition of these RF revealed that 82% of the IgM RF used kappa L chains whereas only 31% of the non-IgM RF used kappa chains. Antigen-binding analyses of these RF revealed that all the synovial tissue-derived RF from the advanced RA patient exhibited antigen binding specificities restricted to a narrow range of gamma globulins. In contrast, the synovial RF of the other two patients were either reactive with a broader spectrum of gamma globulins or reactive with a variety of unrelated antigens. In every instance, the gamma globulin-specific RF were of all three major isotypes whereas the polyreactive RF were restricted to the IgM isotype. These data demonstrate that synovial B cells from both RA and OA patients can produce RF and that significant differences can exist among patients in the percentage of RF generated and their H and L chain isotype distribution. The reversal of the kappa:lambda ratio among the IgG and IgA RF and the more restricted antigen-binding specificities of the IgG and IgA vs IgM RF suggest that a non-stochastic, possibly antigen-driven selection process was involved in their generation. The relevance of these differences in RF precursor frequency, H and L chain distribution, and antigen specificity to these two diseases warrants further investigation.
Department of Medicine, North Shore University Hospital, Manhasset, New York 11030.
S
S
Kaplan
K
K
Hyman
R
R
Brooks
M
M
Wakai
S
S
Hashimoto
R
R
Furie
N
N
Chiorazzi
D000368:Aged; D000911:Antibodies, Monoclonal / Q000276:immunology; D000917:Antibody Formation; D001172:Arthritis, Rheumatoid / Q000378:metabolism; D001402:B-Lymphocytes / Q000378:metabolism / Q000382:microbiology*; D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral; D002999:Clone Cells / Q000378:metabolism; D005260:Female; D004854:Herpesvirus 4, Human / Q000502:physiology*; D006801:Humans; D006825:Hybridomas / Q000378:metabolism; D007070:Immunoglobulin A / Q000737:chemistry*; D007074:Immunoglobulin G / Q000737:chemistry*; D007075:Immunoglobulin M / Q000737:chemistry*; D010003:Osteoarthritis / Q000378:metabolism; D012217:Rheumatoid Factor / Q000032:analysis* / Q000378:metabolism; D013583:Synovial Membrane / Q000166:cytology / Q000382:microbiology
D000911:Antibodies, Monoclonal; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D012217:Rheumatoid Factor