MONOMORPHIC ORGANIZATION OF HUMAN-DIVERSITY (DH) HEAVY-CHAIN VARIABLE GENES

While recent evidence indicates that human immunoglobulin heavy chain variable (V(H)) genes exhibit a high degree of heterogeneity, little is known concerning the polymorphism of the diversity (D(H)) gene complex. This locus comprises two clusters, major and minor, which are physically linked with the V(H) locus. In assessing the variability of the human major and minor D(H) clusters, we found no evidence for a substantial restriction site polymorphism. We also noted that, in contrast to what was found in the Japanese population, the D(H)1 gene is not deleted in an appreciable proportion of the European population. We propose that, because D(H) genes impart the critical functions associated with the third complementarity-determining region, the genomic organization of the human D(H) locus has been evolutionarily conserved through selection pressure mechanisms.