SOMATIC MUTATION AND CDR3 LENGTHS OF IMMUNOGLOBULIN-KAPPA LIGHT-CHAINS EXPRESSED IN PATIENTS WITH RHEUMATOID-ARTHRITIS AND IN NORMAL INDIVIDUALS

Immunoglobulin secretion by plasma cells infiltrating synovial membran es is a prominent feature of RA, Previous analyses of a cDNA library g enerated from synovium of RA patient BC revealed immunoglobulin kappa light chain transcripts with extensive somatic mutation, frequent N re gion addition, and unexpected variation in the lengths of CDR3 regions which form the center of the antigen binding site, To determine if th ese characteristics are present in other individuals, we performed rev erse transcription-polymerase chain reaction amplification and sequenc ed greater than or equal to 10 V kappa-containing amplicons from nine tissue samples: synovia of three individuals with long-standing RA (in cluding patient BC), PBLs of two of these individuals, and PBLs or spl enocytes of four normal individuals. Increased levels of somatic mutat ion in PBLs appeared to correlate with increased age, which may reflec t accumulation of circulating memory cells and/or decreased bone marro w production of naive B lymphocytes. Two of three RA synovial samples and both RA PBL samples exhibited increased proportions of clones with unusual CDR3 lengths, Enrichment for these antibody binding sites cou ld be due to abnormal regulation of the emerging repertoire or to sele ction for B lymphocytes bearing antibodies of unusual specificity, and may play a role in the pathogenesis of RA.