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 discer n the contributions of genetic, versus environmental factors on expres sed traits, In the present experiments, we applied a novel anchored PC R-ELISA system to compare the heavy chain V gene (V-H) subgroup repert oires of mu and gamma expressing B lymphocytes from ten pairs of adult monozygotic twins, including eight pairs who are concordant or discor dant 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, monozy gotic twins who are discordant for RA also use highly similar IgM V-H gene-subgroup repertoires. Finally, the V-H gene repertoire remained s table over time. Collectively these data reveal that genetic factors p redominantly control V-H gene repertoire formation.