We investigated the somatic mutational pattern of a specific Vlambda light chain variable region (V) gene in rheumatoid arthritis (RA) patients. The Vlambda4B light chain was chosen because of its location on the lambda locus and because of its previously observed use in IgM rheumatoid factors.
We sequenced 13 different mRNA transcripts of Vlambda4B from the synovium of three different RA patients. These were compared to 31 identifiable Vlambda4B sequences from GenBank, which were obtained from the PBL of patients without RA.
A subset of Vlambda4B 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 Vlambda4B displayed frequent replacement mutations but did not possess any silent mutations.
The hypermutation of RA synovial-derived Vlambda4B sequences, especially in the framework areas, may contribute to or may be the result of altered mutational mechanisms and/or prolonged B cell life.