Mutational Analysis of Immunoglobulin Germline Derived Vλ4B Light Chains in Rheumatoid Arthritis

Objective: We investigated the somatic mutational pattern of a specific Vλ light chain variable region (V) gene in rheumatoid arthritis (RA) patients. The Vλ4B light chain was chosen because of its location on the λ locus and because of its previously observed use in IgM rheumatoid factors. Methods: We sequenced 13 different mRNA transcripts of Vλ4B from the synovium of three different RA patients. These were compared to 31 identifiable Vλ4B sequences from GenBank, which were obtained from the PBL of patients without RA. Results: A subset of Vλ4B had a high rate of mutation, especially in the framework regions within the RA synovium. Furthermore, a set of codons within the first complementary determining region of Vλ4B displayed frequent replacement mutations but did not possess any silent mutations. Conclusion: The hypermutation of RA synovial-derived Vλ4B sequences, especially in the framework areas, may contribute to or may be the result of altered mutational mechanisms and/or prolonged B cell life.