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

Abstract

The structure of the human V kappa locus has been thoroughly investigated, but how the germ-line V kappa gene segment repertoire is actually sampled in kappa chain gene rearrangements is not known. In order to begin to answer this question we have polymerase chain reaction (PCR) amplified the rearranged V kappa genes from 26 kappa-expressing cases of chronic lymphocytic leukemia (CLL), followed by cloning and sequencing of the PCR product. All four V kappa 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 V kappa genes, indicating that no somatic mutation has occurred. Of the remaining 7 rearranged V kappa 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-quarters of cases the rearranged genes are unmutated; (b) there is preferential usage of individual V kappa genes but not of V kappa gene families; and (c) the V kappa genes used are widely dispersed in the V kappa locus.

Chronic lymphocytic leukemia B cells express restricted sets of mutated and unmutated antigen receptors.

“…Specifically, it has been assumed that B-CLL cells would accumulate little, if any, somatic mutation. This notion has been supported by several studies (10)(11)(12)(13)(14)(15)(16)(17) and challenged by others (18)(19)(20)(21)(22).…”

Analysis of Vκ genes in rheumatoid arthritis (RA) synovial B lymphocytes provides evidence for both polyclonal activation and antigen-driven selection

“…The third V I-expressing hybridoma, A3D5, was 99 . 7% homologous to the O8 germ-line gene, which is frequently expressed in responses to DNA, thyroglobulin and in B cells from patients with CLL [29,30,43], but the antibody did not react with any antigen.…”

“…Two of the three V I genes (A2A2 and A1B4) were homologous with the O12-O2 gene, which is frequently expressed in responses to both self and exogenous antigens and in B cells from patients with CLL [30,41,43]. However, only A2A2 reacted with IgG.…”

Heterogeneity in junctional regions of immunoglobulin kappa deleting element rearrangements in B cell leukemias: a new molecular target for detection of minimal residual disease

“…[42][43][44][45][46] But with the discovery of the PCR technique the analysis of antigen specific receptor gene rearrangements as well as the analysis of IGK gene rearrangements is moving rapidly. [47][48][49][50][51][52][53][54][55][56] However, reports about V gene usage in Kde rearrangements are not available. V family usage (VI-IV) in our Kde rearrangements was compared with V family usage in V-J rearrangements as reported in the literature and summarized in Table 4.…”