A uniform deleting element mediates the loss of kappa genes in human B cells
- PMID: 3927169
- DOI: 10.1038/316260a0
A uniform deleting element mediates the loss of kappa genes in human B cells
Abstract
Human immunoglobulin light-chain genes become rearranged in an ordered fashion during pre-B-cell development such that rearrangement generally occurs in kappa genes before lambda genes (refs 1,2). This ordered process includes an unanticipated deletion of the constant kappa (C kappa) gene and kappa enhancer sequence which precedes lambda rearrangement, and the site of this deletional recombination was located 3' to the joining (J kappa) segments in 75% of cases studied. We have now characterized the recombinational element responsible for this event on three separate alleles and found them to be identical. This kappa-deleting element recombined site-specifically with a palindromic signal (CACAGTG) located in the J kappa-C kappa intron. All losses of C kappa genes in other human B cells were mediated by this determinant, including the 25% of instances when this element recombined with sequences 5' to J kappa. In contrast, the kappa-deleting element remained in its germline form on all successful kappa-producing alleles. Moreover, kappa loss is an evolutionarily conserved event, as the kappa-deleting element appears to be the human homologue of the murine RS sequence. Our results suggest that this element may help ensure isotypic and allelic exclusion of light chains and may be involved in the ordered use of human light-chain genes.
Similar articles
-
Human immunoglobulin kappa light-chain genes are deleted or rearranged in lambda-producing B cells.Nature. 1981 Apr 2;290(5805):368-72. doi: 10.1038/290368a0. Nature. 1981. PMID: 6783958
-
Deletions of kappa chain constant region genes in mouse lambda chain-producing B cells involve intrachromosomal DNA recombinations similar to V-J joining.Proc Natl Acad Sci U S A. 1985 Sep;82(18):6211-5. doi: 10.1073/pnas.82.18.6211. Proc Natl Acad Sci U S A. 1985. PMID: 3929252 Free PMC article.
-
Normal human B cells display ordered light chain gene rearrangements and deletions.J Exp Med. 1982 Oct 1;156(4):975-85. doi: 10.1084/jem.156.4.975. J Exp Med. 1982. PMID: 6818320 Free PMC article.
-
Lambda chains and genes in inbred mice.Annu Rev Immunol. 1985;3:337-65. doi: 10.1146/annurev.iy.03.040185.002005. Annu Rev Immunol. 1985. PMID: 3933530 Review. No abstract available.
-
Comparative Aspects of Immunoglobulin Gene Rearrangement Arrays in Different Species.Front Immunol. 2022 Feb 11;13:823145. doi: 10.3389/fimmu.2022.823145. eCollection 2022. Front Immunol. 2022. PMID: 35222402 Free PMC article. Review.
Cited by
-
Establishing Simultaneous T Cell Receptor Excision Circles (TREC) and K-Deleting Recombination Excision Circles (KREC) Quantification Assays and Laboratory Reference Intervals in Healthy Individuals of Different Age Groups in Hong Kong.Front Immunol. 2020 Jul 16;11:1411. doi: 10.3389/fimmu.2020.01411. eCollection 2020. Front Immunol. 2020. PMID: 32765500 Free PMC article.
-
MYC oncogene involved in a t(8;22) chromosome translocation is not altered in its putative regulatory regions.Proc Natl Acad Sci U S A. 1987 May;84(9):2824-8. doi: 10.1073/pnas.84.9.2824. Proc Natl Acad Sci U S A. 1987. PMID: 3033665 Free PMC article.
-
Mechanism of the t(14;18) chromosomal translocation: structural analysis of both derivative 14 and 18 reciprocal partners.Proc Natl Acad Sci U S A. 1987 Apr;84(8):2396-400. doi: 10.1073/pnas.84.8.2396. Proc Natl Acad Sci U S A. 1987. PMID: 3104914 Free PMC article.
-
Viral involvement in Hodgkin's disease: detection of clonal type A Epstein-Barr virus genomes in tumour samples.Br J Cancer. 1991 Aug;64(2):227-32. doi: 10.1038/bjc.1991.281. Br J Cancer. 1991. PMID: 1654072 Free PMC article.
-
Continuing rearrangement but absence of somatic hypermutation in immunoglobulin genes of human B cell precursor leukemia.J Exp Med. 1988 Jul 1;168(1):229-45. doi: 10.1084/jem.168.1.229. J Exp Med. 1988. PMID: 2840480 Free PMC article.
MeSH terms
Substances
Associated data
- Actions
- Actions
LinkOut - more resources
Full Text Sources
Other Literature Sources