Analysis of Ig kappa light chain gene variable regions expressed in the rheumatoid synovial B cells.
Sequence analysis of antibody variable (V) regions can provide an insight regarding whether B cells have gone through an antigen-driven process of affinity maturation. In this study, we analyzed 16 V-regions of immunoglobulin (Ig) kappa light chain genes obtained from a cDNA library of a rheumatoid arthritis (RA) synovial tissue. A salient feature of our results is the high frequency utilization of germline V kappa I family genes, especially the O2/O12 gene (38%). All kappa V-regions showed extensive somatic hypermutation with 5.4% of an average mutation rate. Replacement to silent mutation (R/S) ratio in the complementarity determining region (CDR) was > 2.9 in 12 out of 16 clones, indicating that the majority of the RA synovial B cells had undergone affinity maturation. However, the four other clones showed R/S ratios of < 2.9 in the CDR despite a high mutation rate. In contrast to the previous reports, long CDR3 was not a characteristic feature of these clones. In summary, these data show the high frequency utilization of the germline O2/O12 gene and a high rate of mutation with an evidence of antigen selection in most of the Ig kappa genes expressed in the RA synovium.
Pyon
H S
HS
Graduate School of Biotechnology, Korea University, Seoul 136-701.
Ha-Lee
Y M
YM
Song
G G
GG
Sohn
J
J
D001172:Arthritis, Rheumatoid / Q000276:immunology*; D001483:Base Sequence; D022801:Complementarity Determining Regions / Q000235:genetics; D005260:Female; D015328:Gene Rearrangement, B-Lymphocyte, Light Chain; D005803:Genes, Immunoglobulin; D018095:Germ-Line Mutation; D006801:Humans; D007144:Immunoglobulin J-Chains / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D007145:Immunoglobulin kappa-Chains / Q000235:genetics*; D008875:Middle Aged; D013583:Synovial Membrane / Q000276:immunology*
D022801:Complementarity Determining Regions; D007144:Immunoglobulin J-Chains; D007135:Immunoglobulin Variable Region; D007145:Immunoglobulin kappa-Chains