The Vϰ gene repertoire in the human germ line

Abstract
The question of how many Vϰ gene segments exist in the human germ line was addressed. Seventy‐five Vϰ genes of the x locus and twenty‐five Vϰ genes localized outside of the locus (“orphons”) had been cloned previously; 67 of the genes and 19 of the orphons had already been sequenced yielding 36 and 1 potentially functional Vϰ genes, respectively, the remaining ones being pseudogenes. We now (a) determined the relative hybridization intensities of the cloned Vϰ genes and orphons, (b) identified the bands in blot hybridizations of genomic DNA digests with the cloned genes and orphons, (c) determined the band intensities in the genomic DNA digests from two individuals and one cell line, (d) normalized the results with the help of the Cϰ gene segment which is present in the haploid genome in one copy, (e) compared the genomic blot hybridization patterns with patterns of equimolar mixtures of the cloned Vϰ genes and orphons, and (f) defined the bands and fractional intensities in bands that could not be assigned to cloned genes or orphons. From the resulting data we conclude that there are 5‐7 still uncloned Vϰ genes in germ‐line DNA in addition to the 75 known Vϰ genes and in addition to the 25 orphons 12‐15 orphon candidates. It appears that the rheumatoid factor light chains of the Wa and 6B6.6 idiotypes are coded for by one VϰIII gene each. It is concluded that the x locus comprises no more than 50 potentially functional genes and no more than 85 Vϰ genes altogether.