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

SUMMARY 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 frequeney 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.