Tj. Semrad et al., Mutational analysis of immunoglobulin germline derived V lambda 4A light chains in rheumatoid arthritis, CLIN IMMUNO, 99(2), 2001, pp. 276-282
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.