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The Size of a Murine Heavy Chain Variable Region Gene Family: Implications for the Magnitude and Evolution of the V_H Locus in Mouse

The problem of how much antibody diversity is encoded in the germline as variable region genes has long been of interest to immunologists. We have measured the size of the J558 V H family in the BALB/c mouse by a probe excess titration method, and found that the family contains approximately 1000 members. As a control for systematic error, we used the same method to measure the number of class I MHC genes in BALB/c. We found that the third domain of the class I D d gene detects 36-40 class I genes. Dot blots and genome blots with copy number controls give results consistent with a J558 family size of 500-1000 V H genes. We note that each band evident on genomic blots of DNA from several mouse strains contains multiple V H genes, and that a significant fraction of these bands are polymorphic among the mouse strains tested. We discuss the implications of this result for both the size and evolution of the V H locus in mouse.