The molecular basis of a VH gene polymorphism that determines the expression of a major idiotype

The strain A immune response to a synthetic antigen (p-azophenylarsonate) is dominated by antibodies bearing an idiotype encoded by VH genes derived from a single germline VH gene segment called VHIdCR (a member of the J558 family). Balb/c mice fail to produce this idiotype. Southern blotting analyses with a probe derived from VHIdCR have shown that differences in patterns of hybridization and in intensity of bands are seen between the two strains. We demonstrate by DNA cloning and sequence analyses that Balb/c mice have no allelic version of VHIdCR. This result constrasts with that reported for interstrain comparisons of VH genes encoding antibodies to environmental pathogens where evolutionary conservation of VH sequence information is seen. We suggest, on the basis of these and earlier results, that domination of the anti-Ars immune response by antibodies encoded by VHIdCR is not the indirect consequence of evolutionary or somatic selection pressures acting on the VHIdCR gene segment.