EVIDENCE OF ANTIGEN RECEPTOR-INFLUENCED OLIGOCLONAL B-LYMPHOCYTE EXPANSION IN THE SYNOVIUM OF A PATIENT WITH LONGSTANDING RHEUMATOID-ARTHRITIS

Plasma cell infiltration of synovium is common in longstanding rheumat oid arthritis( RA). The mechanism(s) underlying synovial B cell prolif eration remains unclear. One theory invokes nonspecific polyclonal sti muli; another implicates antigen as the driving force. Antigen-driven repertoires are characteristically enriched for related sets of V gene segments containing similar sequence in the antigen binding site (com plementarity-determining regions; CDRs). To study the forces shaping B cell proliferation, we analyzed V kappa transcripts expressed in the synovium of an RA patient. We found Humkv325, a developmentally regula ted V kappa III gene segment associated with autoantibody reactivity, in > 10% of randomly-chosen synovial C kappa cDNAs. Two sets of sequen ces contained identical charged amino acid residues at the V kappa-J k appa join, apparently due to N region addition. We generated ''signatu re'' oligonucleotides from these CDR3s and probed PCR amplified V kapp a products from the synovium and PBLs of the same patient, and from PB Ls and spleen of individuals without rheumatic disease. Significant ex pression of transcripts containing these unique CDR3 sequences occurre d only in the patient's synovium. Thus, in this synovium there is expa nsion of a limited set of B cell clones expressing antigen receptors t hat bear evidence of antigen selection.