Human immunoglobulin heavy-chain-variable (VH) region gene families defined by hybridization with cloned human and murine VH-genes

Abstract

The Southern DNA hybridization technique was used to determine the organization of human immunoglobulin heavy-chain-variable region (VH) gene families and the extent of polymorphism within these families. Human DNA was digested with a restriction enzyme and then hybridized to a cloned human or murine VH gene. Six human and six murine genes were used. Hybridization patterns seen in the human genes fell into three groups, which corresponded to the Kabat subgroup assignments based on sequence. When DNA from different individuals was compared, polymorphism was demonstrated in each of the three gene families. The VH II family demonstrated a higher degree of polymorphism than the others. Hybridization with the murine probes, each of which represented a different murine VH-gene family, revealed six distinct patterns of hybridization. Five of the probes detected all or a portion of one of the previously defined human families. The sixth probe, 36-60, yields a unique pattern of hybridization, suggesting a fourth VH-gene family. Dot hybridizations show that 36-60 does not hybridize with human VH-genes representing each of the known families, further supporting this possibility.