Immunoglobulin heavy chain variable region gene utilization by B cell hybridomas derived from rheumatoid synovial tissue

Abstract

Rheumatoid arthritis (RA) is a chronic inflammatory disease that primarily affects synovial joints. Activated B lymphocytes and plasma cells are present in the synovial tissue and are thought to contribute to the immunopathology of the rheumatoid joint. To investigate rheumatoid synovial B lymphocytes, we have generated B cell hybridomas from synovial tissue of an RA patient. Here we describe the immunoglobulin V(H) gene repertoire of eight IgM- and 10 IgG-secreting synovial-derived hybridomas. The V(H)4 gene family is highly represented (38.5%) in this panel of hybridomas compared with the frequency of V(H)4 gene expression in circulating B lymphocytes reported previously (19-22%) and with the V(H)4 gene frequency we observed in a panel of hybridomas derived in the same manner from the spleen and tonsil of normal individuals (19%). The increased frequency of V(H)4 gene expression was not due to the expansion of a single B cell clone in vivo as none of these hybridomas was clonally related. Two synovial-derived hybridomas secreted autoantibodies; one (V(H)3+) secreted an IgM-rheumatoid factor (RF) and the other (V(H)4+) secreted IgM with polyreactive binding to cytoskeletal proteins and cardiolipin. The antibodies secreted by the remaining synovial-derived hybridomas were not reactive with the autoantigens tested. The V(H) gene usage in a proportion (5/17) of synovial-derived hybridomas that expressed CD5 antigen provided preliminary evidence that CD5+ B cells in RA synovium have a similar increase of V(H)4 gene expression reported for CD5+ B cells from normal individuals and patients with chronic lymphocytic leukaemia.