The human immunoglobulin V(H) gene repertoire is genetically controlled and unaltered by chronic autoimmune stimulation.
The factors controlling immunoglobulin (Ig) gene repertoire formation are poorly understood. Studies on monozygotic twins have helped discern the contributions of genetic versus environmental factors on expressed traits. In the present experiments, we applied a novel anchored PCR-ELISA system to compare the heavy chain V gene (V(H)) subgroup repertoires of mu and gamma expressing B lymphocytes from ten pairs of adult monozygotic twins, including eight pairs who are concordant or discordant for rheumatoid arthritis. The results disclosed that the relative expression of each Ig V(H) gene subgroup is not precisely proportional to its relative genomic size. The monozygotic twins had more similar IgM V(H) gene repertoires than did unrelated subjects. Moreover, monozygotic twins who are discordant for RA also use highly similar IgM V(H) gene-subgroup repertoires. Finally, the V(H) gene repertoire remained stable over time. Collectively, these data reveal that genetic factors predominantly control V(H) gene repertoire formation.
Kohsaka
H
H
Division of Immunological Diseases, Medical Research Institute, Tokyo Medical and Dental University, Japan. kohsaka.imm@tmd.ac.jp
Carson
D A
DA
Rassenti
L Z
LZ
Ollier
W E
WE
Chen
P P
PP
Kipps
T J
TJ
Miyasaka
N
N
D000328:Adult; D000368:Aged; D001168:Arthritis / Q000378:metabolism; D015551:Autoimmunity / Q000276:immunology*; D001402:B-Lymphocytes / Q000378:metabolism; D015342:DNA Probes / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D007135:Immunoglobulin Variable Region / Q000235:genetics / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D017421:Sequence Analysis; D014158:Transcription, Genetic / Q000235:genetics; D014430:Twins, Monozygotic / Q000235:genetics
D015342:DNA Probes; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007135:Immunoglobulin Variable Region