DIFFERENTIAL USE OF IMMUNOGLOBULIN LIGHT-CHAIN GENES AND B-LYMPHOCYTEEXPANSION AT SITES OF DISEASE IN RHEUMATOID-ARTHRITIS (RA) COMPARED WITH CIRCULATING B-LYMPHOCYTES

The presence of germinal centre-like structures and clonotypic expansi on of lymphocytes in RA synovia may indicate a site-specific immune re sponse to local antigens, rather than passively entrapped immune cells , that sustains synovial inflammation. in this study we compare the na ture of immunoglobulin light chain variable region gene use in the syn ovium of RA patients with peripheral B cells to determine the nature o f the synovial immune response. Using V lambda and V kappa gene finger printing, which relies on differences in CDR3 length, we demonstrate d ifferences in the pattern of V lambda and V kappa use and clonotypic e xpansion of B cells between the synovium and peripheral blood of RA pa tients. Further, we show that some synovial rearrangements with long C DR3 are selectively expanded. These longer than usual CDR3 were genera ted by a number of mechanisms including N-additions. However, the obse rved differences were not uniform in different patients. These observa tions suggest that local synovial antigens drive significant numbers o f T and B lymphocytes selected from an existing repertoire shaped by g enetic and environmental factors. Further, the data argue against pass ive retention of most B cells in the synovium of RA patients.