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PMID: 3141924 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Physical linkage of a human immunoglobulin heavy chain variable region gene segment to diversity and joining region elements.

Schroeder HW, Walter MA, Hofker MH, Ebens A, Willems van Dijk K, Liao LC, Cox DW, Milner EC, Perlmutter RM

Abstract

Antibody genes are assembled from a series of germ-line gene segments that are juxtaposed during the maturation of B lymphocytes. Although diversification of the adult antibody repertoire results in large part from the combinatorial joining of these gene segments, a restricted set of antibody heavy chain variable (VH), diversity (DH), and joining (JH) region gene segments appears preferentially in the human fetal repertoire. We report here that one of these early-expressed VH elements (termed VH6) is the most 3' VH gene segment, positioned 77 kilobases on the 5' side of the JH locus and immediately adjacent to a set of previously described DH sequences. In addition to providing a physical map linking human VH, DH, and JH elements, these results support the view that the programmed development of the antibody VH repertoire is determined in part by the chromosomal position of these gene segments.

MeSH Terms
B-Lymphocytes/analysis Base Sequence Cosmids Genes, Immunoglobulin Genetic Linkage Humans Immunoglobulin Heavy Chains/genetics Immunoglobulin Variable Region/genetics Molecular Sequence Data
Chemicals
Immunoglobulin Heavy Chains Immunoglobulin Variable Region
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Schroeder H W
Howard Hughes Medical Institute, University of Washington, Seattle 98195.
Walter M A
Hofker M H
Ebens A
Willems van Dijk K
Liao L C
Cox D W
Milner E C
Perlmutter R M
References (30)
30 references, click to expand
  1. The B cell specificity repertoire: its relationship to definable subpopulations.
    Transplant Rev. 1975;24:41-83 PMID: 49962
  2. Structure of the human immunoglobulin mu locus: characterization of embryonic and rearranged J and D genes.
    Cell. 1981 Dec;27(3 Pt 2):583-91 PMID: 6101209
  3. Somatic generation of antibody diversity.
    Nature. 1983 Apr 14;302(5909):575-81 PMID: 6300689
  4. Diversity and joining segments of mouse immunoglobulin heavy chain genes are closely linked and in the same orientation: implications for the joining mechanism.
    Proc Natl Acad Sci U S A. 1983 May;80(10):3030-4 PMID: 6407007
  5. New M13 vectors for cloning.
    Methods Enzymol. 1983;101:20-78 PMID: 6310323
  6. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity.
    Anal Biochem. 1983 Jul 1;132(1):6-13 PMID: 6312838
  7. Multiple VH gene segments encode murine antistreptococcal antibodies.
    J Exp Med. 1984 Jan 1;159(1):179-92 PMID: 6420495
  8. Double cos site vectors: simplified cosmid cloning.
    Gene. 1983 Dec;26(2-3):137-46 PMID: 6323255
  9. Structure of the 5' ends of immunoglobulin genes: a novel conserved sequence.
    Proc Natl Acad Sci U S A. 1984 May;81(9):2650-4 PMID: 6425835
  10. The immunoglobulin heavy chain variable region (Igh-V) locus in the mouse. I. One hundred Igh-V genes comprise seven families of homologous genes.
    Eur J Immunol. 1984 Oct;14(10):922-30 PMID: 6092095
  11. Preferential utilization of the most JH-proximal VH gene segments in pre-B-cell lines.
    Nature. 1984 Oct 25-31;311(5988):727-33 PMID: 6092962
  12. Developmentally controlled expression of immunoglobulin VH genes.
    Science. 1985 Mar 29;227(4694):1597-601 PMID: 3975629
  13. Transcription cell type specificity is conferred by an immunoglobulin VH gene promoter that includes a functional consensus sequence.
    Cell. 1985 Jun;41(2):479-87 PMID: 3921262
  14. Immunoglobulin genes.
    Annu Rev Immunol. 1983;1:499-528 PMID: 6443559
  15. Analysis of cosmids using linearization by phage lambda terminase.
    Gene. 1985;40(2-3):259-66 PMID: 3007292
  16. Specific-primer-directed DNA sequencing.
    Anal Biochem. 1986 Apr;154(1):353-60 PMID: 3010776
  17. Regulation of the assembly and expression of variable-region genes.
    Annu Rev Immunol. 1986;4:339-68 PMID: 3085692
  18. Mapping of the class II region of the human major histocompatibility complex by pulsed-field gel electrophoresis.
    Nature. 1986 Oct 2-8;323(6087):453-5 PMID: 3020430
  19. Development of additional RFLP probes near the locus for Duchenne muscular dystrophy by cosmid cloning of the DXS84 (754) locus.
    Hum Genet. 1986 Nov;74(3):270-4 PMID: 2877935
  20. Organization and evolution of variable region genes of the human immunoglobulin heavy chain.
    J Mol Biol. 1986 Aug 20;190(4):529-41 PMID: 3097326
  21. Adult B-cell repertoire is biased toward two heavy-chain variable-region genes that rearrange frequently in fetal pre-B cells.
    Proc Natl Acad Sci U S A. 1987 Apr;84(8):2454-8 PMID: 3104915
  22. Programmed development of the antibody repertoire.
    Curr Top Microbiol Immunol. 1987;135:95-109 PMID: 3107915
  23. A novel family of variable region genes of the human immunoglobulin heavy chain.
    J Mol Biol. 1987 Jun 20;195(4):761-8 PMID: 3116265
  24. Early restriction of the human antibody repertoire.
    Science. 1987 Nov 6;238(4828):791-3 PMID: 3118465
  25. Human heavy-chain variable region gene family nonrandomly rearranged in familial chronic lymphocytic leukemia.
    Proc Natl Acad Sci U S A. 1987 Dec;84(23):8563-7 PMID: 3120193
  26. Analysis of genetic variation reveals human immunoglobulin VH-region gene organization.
    Am J Hum Genet. 1988 Mar;42(3):446-51 PMID: 2894757
  27. Content and organization of the human Ig VH locus: definition of three new VH families and linkage to the Ig CH locus.
    EMBO J. 1988 Mar;7(3):727-38 PMID: 3396540
  28. Dispersed localization of D segments in the human immunoglobulin heavy-chain locus.
    EMBO J. 1988 Apr;7(4):1047-51 PMID: 2841108
  29. Structure of the murine lck gene and its rearrangement in a murine lymphoma cell line.
    Mol Cell Biol. 1988 Aug;8(8):3058-64 PMID: 2850479
  30. Human immunoglobulin D segments encoded in tandem multigenic families.
    Nature. 1981 Dec 17;294(5842):631-5 PMID: 7312051
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
Published
1988-11-00
Pages
8196-200
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC282394
Subset
IM
Databases
GENBANK
J04097
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