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. 1988 Feb 1;167(2):488–501. doi: 10.1084/jem.167.2.488

The kappa-deleting element. Germline and rearranged, duplicated and dispersed forms

PMCID: PMC2188845  PMID: 3126251

Abstract

Human light chain genes are used in a kappa before lambda order. Accompanying this hierarchy is the rearrangement of a kappa-deleting element (Kde) which eliminates the kappa locus before lambda gene rearrangement. In approximately 60% of rearrangements the Kde recombines at a conserved heptamer within the J kappa-C kappa intron. We demonstrated that aberrant V/J rearrangements possessing apparent "N" nucleotides existed 5' to the J kappa-Kde rearrangements. This suggests that the Kde may selectively eliminate nonfunctional V/J alleles. A kappa-producing cell that displayed the unusual finding of lambda gene rearrangement demonstrated a rearranged Kde. This rearrangement was a V kappa/Kde recombination and the heptamer-11 bp spacer-nonamer flanking the V kappa is the target site of the Kde 40% of the time. The mouse possesses a counterpart to the Kde (recombining sequence [RS]) and the highly conserved regions surround the heptamer- spacer-nonamer signals. No complete protein product was predicted from the germline Kde near its break-point and no consistent fusion product was predicted from either the V/Kde or V/J-Kde rearrangements. A distal portion of the Kde is duplicated and is present at 2q11 as well as 2p11. The evolutionary conservation of the kappa-elimination event, the duplication and maintenance of the Kde indicates that it has a function. A portion of the Kde may still prove to encode a trans-acting factor that directly affects lambda rearrangement. A certain role for the Kde is its site-specific rearrangement, which destroys ineffective kappa genes and sets the stage for lambda gene utilization.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Alt F. W., Enea V., Bothwell A. L., Baltimore D. Activity of multiple light chain genes in murine myeloma cells producing a single, functional light chain. Cell. 1980 Aug;21(1):1–12. doi: 10.1016/0092-8674(80)90109-9. [DOI] [PubMed] [Google Scholar]
  2. Alwine J. C., Kemp D. J., Parker B. A., Reiser J., Renart J., Stark G. R., Wahl G. M. Detection of specific RNAs or specific fragments of DNA by fractionation in gels and transfer to diazobenzyloxymethyl paper. Methods Enzymol. 1979;68:220–242. doi: 10.1016/0076-6879(79)68017-5. [DOI] [PubMed] [Google Scholar]
  3. Coleclough C., Perry R. P., Karjalainen K., Weigert M. Aberrant rearrangements contribute significantly to the allelic exclusion of immunoglobulin gene expression. Nature. 1981 Apr 2;290(5805):372–378. doi: 10.1038/290372a0. [DOI] [PubMed] [Google Scholar]
  4. Desiderio S. V., Yancopoulos G. D., Paskind M., Thomas E., Boss M. A., Landau N., Alt F. W., Baltimore D. Insertion of N regions into heavy-chain genes is correlated with expression of terminal deoxytransferase in B cells. Nature. 1984 Oct 25;311(5988):752–755. doi: 10.1038/311752a0. [DOI] [PubMed] [Google Scholar]
  5. Durdik J., Moore M. W., Selsing E. Novel kappa light-chain gene rearrangements in mouse lambda light chain-producing B lymphocytes. Nature. 1984 Feb 23;307(5953):749–752. doi: 10.1038/307749a0. [DOI] [PubMed] [Google Scholar]
  6. Feinberg A. P., Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. doi: 10.1016/0003-2697(83)90418-9. [DOI] [PubMed] [Google Scholar]
  7. Gunning P., Ponte P., Okayama H., Engel J., Blau H., Kedes L. Isolation and characterization of full-length cDNA clones for human alpha-, beta-, and gamma-actin mRNAs: skeletal but not cytoplasmic actins have an amino-terminal cysteine that is subsequently removed. Mol Cell Biol. 1983 May;3(5):787–795. doi: 10.1128/mcb.3.5.787. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hieter P. A., Korsmeyer S. J., Waldmann T. A., Leder P. Human immunoglobulin kappa light-chain genes are deleted or rearranged in lambda-producing B cells. Nature. 1981 Apr 2;290(5805):368–372. doi: 10.1038/290368a0. [DOI] [PubMed] [Google Scholar]
  9. Klobeck H. G., Zachau H. G. The human CK gene segment and the kappa deleting element are closely linked. Nucleic Acids Res. 1986 Jun 11;14(11):4591–4603. doi: 10.1093/nar/14.11.4591. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Korsmeyer S. J., Hieter P. A., Ravetch J. V., Poplack D. G., Waldmann T. A., Leder P. Developmental hierarchy of immunoglobulin gene rearrangements in human leukemic pre-B-cells. Proc Natl Acad Sci U S A. 1981 Nov;78(11):7096–7100. doi: 10.1073/pnas.78.11.7096. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Korsmeyer S. J., Hieter P. A., Sharrow S. O., Goldman C. K., Leder P., Waldmann T. A. Normal human B cells display ordered light chain gene rearrangements and deletions. J Exp Med. 1982 Oct 1;156(4):975–985. doi: 10.1084/jem.156.4.975. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Moore M. W., Durdik J., Persiani D. M., Selsing E. 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):6211–6215. doi: 10.1073/pnas.82.18.6211. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Morton C. C., Kirsch I. R., Taub R., Orkin S. H., Brown J. A. Localization of the beta-globin gene by chromosomal in situ hybridization. Am J Hum Genet. 1984 May;36(3):576–585. [PMC free article] [PubMed] [Google Scholar]
  14. O'Brien S. J., Nash W. G., Goodwin J. L., Lowy D. R., Chang E. H. Dispersion of the ras family of transforming genes to four different chromosomes in man. Nature. 1983 Apr 28;302(5911):839–842. doi: 10.1038/302839a0. [DOI] [PubMed] [Google Scholar]
  15. Persiani D. M., Durdik J., Selsing E. Active lambda and kappa antibody gene rearrangement in Abelson murine leukemia virus-transformed pre-B cell lines. J Exp Med. 1987 Jun 1;165(6):1655–1674. doi: 10.1084/jem.165.6.1655. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Siminovitch K. A., Bakhshi A., Goldman P., Korsmeyer S. J. A uniform deleting element mediates the loss of kappa genes in human B cells. Nature. 1985 Jul 18;316(6025):260–262. doi: 10.1038/316260a0. [DOI] [PubMed] [Google Scholar]
  18. Siminovitch K. A., Moore M. W., Durdik J., Selsing E. The human kappa deleting element and the mouse recombining segment share DNA sequence homology. Nucleic Acids Res. 1987 Mar 25;15(6):2699–2705. doi: 10.1093/nar/15.6.2699. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Young R. A., Davis R. W. Efficient isolation of genes by using antibody probes. Proc Natl Acad Sci U S A. 1983 Mar;80(5):1194–1198. doi: 10.1073/pnas.80.5.1194. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Yunis J. J., Prakash O. The origin of man: a chromosomal pictorial legacy. Science. 1982 Mar 19;215(4539):1525–1530. doi: 10.1126/science.7063861. [DOI] [PubMed] [Google Scholar]

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