Vχ gene segments rearranged in chronic lymphocytic leukemia are distributed over a large portion of the Vχ locus and do not show somatic mutation

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Abstract
The structure of the human Vχ locus has been thoroughly investigated, but how the germ-line Vχ gene segment repertoire is actually sampled in χ chain gene rearrangements is not known. In order to begin to answer this question we have polymerase chain reaction (PCR) amplified the rearranged Vχ genes from 26χ-expressing cases of chronic lymphocytic leukemia (CLL), followed by cloning and sequencing of the PCR product. All four Vχ gene families were represented amongst rearranged genes. In 25 out of 32 cases, the sequence of the rearranged gene matches perfectly that of 1 of 11 different known germ-line Vχ genes, indicating that no somatic mutation has occurred. Of the remaining 7 rearranged Vχ genes, 4 differ from known germ-line genes by only one or two amino acid residues; and 3 differ from each other and from all known sequences by 5 or more residues, suggesting that somatic mutation has occurred in these 3 cases. We conclude that: (a) in at least three-squarters of cases the rearranged genes are unmutated; (b) there is preferential usage of individual Vχ genes but not of Vχ gene families; and (c) the Vχ genes used are widely dispersed in the Vχ locus.