Polymorphism of germ-line immunoglobulin VH genes correlates with allotype and idiotype markers

The polymorphic nature of the immunoglobulin VH genes was investigated by Southern blot analysis of liver DNA of sixteen different mouse strains and hybridization with VH probes. Differences in restriction enzyme pattern (REP) were observed and six different patterns of restriction fragments were found for the sixteen strains analyzed. No equivalent polymorphism was observed in another multigene family, the actins. The six patterns correlate with immunoglobin constant region allotypes (Igh-1). Experiments with Igh-1-congenic strains suggest that the VH REP is linked to immunoglobulin constant region haplotype. Mouse strains which share inherited idiotypes also share identical VH restriction pattern. This provides a structural basis for the genetic linkage between idiotypes and allotypes. It also indicates that different strains carry different VH gene repertoires, which may be the basis for the expression of different inherited idiotypes in various strains. We propose that a VH group in a set of linked genes that are coinherited as a cluster with the constant region genes and that VH and Ch can be regarded as an extended haplotype.