Immunoglobulin VH region genes of the mouse are organized in overlapping clusters

Restriction fragment length polymorphism has been compared between the Igh loci of C57BL/6 and MOLF/EI (Mus musculus molossinus) mice utilizing probes which detect the C gamma 2b gene and genes from nine VH-gene families. Distinct restriction site patterns were found for the CH genes and for VH families PC7183, Q52 and X24. VH families V31 and J558 showed identical patterns. Mixed patterns of identical and distinct bands were detected in VH families S107, J606, V3660 and VGAM3.8. This indicates that a recombination took place involving the Igh loci of a M. m. molossinus and a progenitor of the C57BL/6 strain. The breakpoint of recombination maps to the chromosomal region carrying VH families S107, J606, VGAM3.8 and V3660. VH families PC7183, Q52 and X24 map 3' to the recombination breakpoint and proximal to the DH-JH-CH region, whereas VH families V31 and J558 accordingly map 5' to the recombination breakpoint and distal to DH-JH-CH. This order of VH families was confirmed by deletion mapping utilizing hybridomas which are haploid either for the Ighb or for the Igha locus. The mapping data indicate that the VH families of the mouse are organized in overlapping clusters. This notion is confirmed by demonstration of the physical linkage of VH genes from families V31 and J558 in the Igha locus.