Analysis of Ig kappa light chain gene variable regions expressed in the rheumatoid synovial B cells

Sequence analysis of antibody variable (V) regions can provide an insight r egarding whether B cells have gone through an antigen-driven process of aff inity maturation. In this study, we analpzed 16 V-regions of immunoglobulin (Ig) kappa light chain genes obtained from a cDNA library of a rheumatoid arthritis (RA) synovial tissue, A salient feature of our results is the hig h frequency utilization of germline V kappaI family genes, especially the O 2/O12 gene (38%). All kappa V-regions showed extensive somatic hypermutatio n with 5.4% of an average mutation rate, Replacement to silent mutation (R/ S) ratio in the complementarity determining region (CDR) was > 2.9 in 12 ou t of 16 clones, indicating that the majority of the RA synovial B cells had undergone affinity maturation. However. the four other clones showed R/S r atios of < 2.9 in the CDR despite a high mutation rate. In contrast to the previous reports, long CDR3 was not a characteristic feature of these clone s. In summary, these data show the high frequency utilization of the germli ne O2/O12 gene and a high rate of mutation with an evidence of antigen sele ction in most of the Ig <kappa> genes expressed in the RA synovium.