Mutational analysis of immunoglobulin germline derived Vlambda4A 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 somatic mutational pattern of the Vlambda4A light chain gene in rheumatoid arthritis (RA) patients. We sequenced 11 different transcripts of Vlambda4A from the synovial tissue of three different RA patients. For comparison, we found 8 rearranged transcripts of Vlambda4A 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 Vlambda4A was noted. Furthermore, conserved replacement mutations in the complementary determining regions, common silent mutations around these replacement mutations, and two subsets of mutated sequences were detected in multiple RA patients. These mutation patterns also correlated with observed consistencies in the rearrangements of the Vlambda4A/Jlambda junction. These data suggest that there is clonal expansion of Vlambda4A light chains in the RA synovium in response to a RA-specific antigen or as the result of an idiotypic response in RA.
Semrad
T J
TJ
Department of Internal Medicine, University of California at Davis, Davis, CA 95616, USA.
Kenny
T P
TP
Malyj
W
W
Robbins
D L
DL
D000368:Aged; D000595:Amino Acid Sequence; D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000276:immunology*; D001483:Base Sequence; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D015328:Gene Rearrangement, B-Lymphocyte, Light Chain; D005803:Genes, Immunoglobulin; D018095:Germ-Line Mutation; D006801:Humans; D007146:Immunoglobulin lambda-Chains / Q000235:genetics*; D008875:Middle Aged; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid
D017931:DNA Primers; D018076:DNA, Complementary; D007146:Immunoglobulin lambda-Chains