Mutational analysis of immunoglobulin germline derived V lambda 4A light chains in rheumatoid arthritis

In order to better characterize the expression of a family of light chains previously expressed in IgM rheumatoid factors, we studied the usage and so matic mutational pattern of the V lambda 4A light chain gene in rheumatoid arthritis (RA) patients. We sequenced 11 different transcripts of V lambda 4A from the synovial tissue of three different RA patients. For comparison, we found 8 rearranged transcripts of V lambda 4A from 4 normal peripheral blood lymphocyte libraries and 1 rearranged transcript from a non-RA con-A- resistant hybridoma in GenBank, A previously undescribed polymorphism of V lambda 4A was noted. Furthermore, conserved replacement mutations in the co mplementary determining regions, common silent mutations around these repla cement mutations, and two subsets of mutated sequences were detected in mul tiple RA patients, These mutation patterns also correlated with observed co nsistencies in the rearrangements of the V lambda 4A/JA junction. These dat a suggest that there is clonal expansion of V lambda 4A tight chains in the RA synovium in response to a RA-specific antigen or as the result of an id iotypic response in RA. (C) 2001 Academic Press.