A DELETION MAP OF THE HUMAN-IMMUNOGLOBULIN HEAVY-CHAIN VARIABLE REGION

Analysis of V(H) gene segments deleted in the process of immunoglobulin heavy chain (IGH) variable region assembly in three series of monoclonal B cell lines has been used to determine the human V(H) region organization. A deletion map of the relative positions of 21 different V(H) gene segments has been determined. The characterization of B cell lines from three unrelated adults of two racial groups yielded the same relative V(H) gene segment order, suggesting that the overall order of V(H) genes in the normal population is constant. This V(H) gene segment order was consistent with what we had previously generated from physical mapping techniques. D(H) segments from the second D(H) cluster, distinct from the major D(H) locus 3' of the V. region, were not observed to be used in 32 different rearrangements. Approximately 77% of the V(H)-(D)J(H) rearrangements involved V(H) gene segments within 500 kb of the J(H) region, indicating that human B cell lines preferentially rearrange J(H)-proximal V(H) gene segments. The switch, observed in mice, from the fetal use of J(H)-proximal V(H) gene segments to an adult V(H) use dependent upon V(H) family size may therefore not occur in humans. This detailed map of the V(H) gene segments is a necessary prerequisite for understanding V(H) usage in development and disease.