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

Sequence analysis of antibody variable (V) regions can provide an insight regarding whether B cells have gone through an antigen-driven process of affinity maturation. In this study, we analyzed 16 V-regions of immunoglobulin (Ig) κ light chain genes obtained from a cDNA library of a rheumatoid arthritis (RA) synovial tissue. A salient feature of our results is the high frequency utilization of germline VκI family genes, especially the O2/O12 gene (38%). All κ V-regions showed extensive somatic hypermutation 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 out 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 ratios 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 clones. In summary, these data show the high frequency utilization of the germline O2/O12 gene and a high rate of mutation with an evidence of antigen selection in most of the Ig κ genes expressed in the RA synovium.