Home LiteratureArticle Details
PMID: 1438216 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Somatic recombination of heavy chain variable region transgenes with the endogenous immunoglobulin heavy chain locus in mice.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 89 ·No. 21 ·1992-11-01 ·Pages 10321-5

Giusti AM, Coffee R, Manser T

Abstract

Transgenic lines of mice were derived by using plasmid constructs containing DNA encoding an antibody heavy chain variable-diversity-joining region (VH-D-JH) and various amounts of 5' and 3' flanking DNA but lacking any repetitive isotype switch (S) or constant (C) region DNA. Unexpectedly, many of the antibody VH regions expressed by B-cell hybridomas generated from immunized transgenic mice were found to be of transgenic origin. Further analyses showed that somatic events had generated hybrid genomic loci in the mice containing the transgenic VH-D-JH gene and plasmid sequences 5' of endogenous heavy chain C region genes. Thus, VH-D-JH transgenes lacking S and C region DNA can recombine with endogenous Igh DNA, leading to the expression of transgene-encoded antibody.

MeSH Terms
Animals Antibodies/blood,genetics Base Sequence Blotting, Southern Cloning, Molecular DNA/genetics,isolation & purification Female Genes, Immunoglobulin Immunoglobulin Heavy Chains/genetics Immunoglobulin Variable Region/genetics Male Mice Mice, Inbred A Mice, Transgenic Molecular Sequence Data Restriction Mapping
Chemicals
Antibodies Immunoglobulin Heavy Chains Immunoglobulin Variable Region DNA
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Giusti A M
Department of Microbiology and Immunology, Jefferson Cancer Institute, Thomas Jefferson Medical College, Philadelphia, PA 19107.
Coffee R
Manser T
References (25)
25 references, click to expand
  1. A mouse immunoglobulin heavy chain deletion mutant: isolation of a cDNA clone and sequence analysis of the mRNA.
    Nucleic Acids Res. 1980 Apr 11;8(7):1475-84 PMID: 6776492
  2. Somatic generation of antibody diversity.
    Nature. 1983 Apr 14;302(5909):575-81 PMID: 6300689
  3. Isotype switching of an immunoglobulin heavy chain transgene occurs by DNA recombination between different chromosomes.
    Cell. 1990 Nov 2;63(3):537-48 PMID: 2121365
  4. Molecular mapping of idiotopes of anti-arsonate antibodies.
    J Immunol. 1986 Apr 1;136(7):2568-74 PMID: 2419442
  5. Evolution of antibody structure during the immune response. The differentiative potential of a single B lymphocyte.
    J Exp Med. 1989 Oct 1;170(4):1211-30 PMID: 2507726
  6. Immunoglobulin gene transcription: molecular mechanisms.
    Trends Genet. 1989 Dec;5(12):395-9 PMID: 2696182
  7. Altered repertoire of endogenous immunoglobulin gene expression in transgenic mice containing a rearranged mu heavy chain gene.
    Cell. 1986 Apr 25;45(2):247-59 PMID: 3084104
  8. A novel VH to VHDJH joining mechanism in heavy-chain-negative (null) pre-B cells results in heavy-chain production.
    Nature. 1986 Aug 28-Sep 3;322(6082):840-2 PMID: 3092105
  9. Mitogen-driven B cell proliferation and differentiation are not accompanied by hypermutation of immunoglobulin variable region genes.
    J Immunol. 1987 Jul 1;139(1):234-8 PMID: 3108398
  10. Evolution of antibody variable region structure during the immune response.
    Immunol Rev. 1987 Apr;96:141-62 PMID: 3298006
  11. The molecular evolution of the immune response: idiotope-specific suppression indicates that B cells express germ-line-encoded V genes prior to antigenic stimulation.
    Eur J Immunol. 1986 Nov;16(11):1439-44 PMID: 3490986
  12. A rapid method for comparing monoclonal antibodies by limited proteolysis and electrophoresis.
    Hybridoma. 1985 Winter;4(4):329-39 PMID: 3905580
  13. Joining of immunoglobulin heavy chain gene segments: implications from a chromosome with evidence of three D-JH fusions.
    Proc Natl Acad Sci U S A. 1982 Jul;79(13):4118-22 PMID: 6287467
  14. The genetic basis of antibody production: a single heavy chain variable region gene encodes all molecules bearing the dominant anti-arsonate idiotype in the strain A mouse.
    Eur J Immunol. 1983 Feb;13(2):123-32 PMID: 6403356
  15. Hybridoma proteins expressing the predominant idiotype of the antiazophenylarsonate response of A/J mice.
    Proc Natl Acad Sci U S A. 1980 Feb;77(2):1120-4 PMID: 6767242
  16. Gene replacement with one-sided homologous recombination.
    Mol Cell Biol. 1992 Jan;12(1):360-7 PMID: 1729610
  17. Limits on heavy chain junctional diversity contribute to the recurrence of an antibody variable region.
    Mol Immunol. 1990 Jun;27(6):503-11 PMID: 2116594
  18. Rapid production of full-length cDNAs from rare transcripts: amplification using a single gene-specific oligonucleotide primer.
    Proc Natl Acad Sci U S A. 1988 Dec;85(23):8998-9002 PMID: 2461560
  19. The mechanism of antigen receptor gene assembly.
    Cell. 1989 Nov 17;59(4):585-8 PMID: 2684413
  20. DNA sequence of the murine gamma 1 switch segment reveals novel structural elements.
    J Immunol. 1986 Apr 1;136(7):2674-83 PMID: 3081649
  21. Recombination between an expressed immunoglobulin heavy-chain gene and a germline variable gene segment in a Ly 1+ B-cell lymphoma.
    Nature. 1986 Aug 28-Sep 3;322(6082):843-6 PMID: 3092106
  22. Sites of switch recombination in IgG2b- and IgG2a-producing hybridomas.
    J Immunol. 1988 May 1;140(9):3219-27 PMID: 3129514
  23. Germ-line transformation of mice.
    Annu Rev Genet. 1986;20:465-99 PMID: 3545063
  24. Fine specificity of idiotope suppression in the A/J anti-azophenylarsonate response.
    J Exp Med. 1983 Feb 1;157(2):795-800 PMID: 6185619
  25. Trans-splicing as a possible molecular mechanism for the multiple isotype expression of the immunoglobulin gene.
    J Exp Med. 1991 Jun 1;173(6):1385-93 PMID: 1903429
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
DOI
10.1073/pnas.89.21.10321
Published
1992-11-01
Pages
10321-5
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC50330
Subset
IM
Grants
NIAID NIH HHS · AI-23739 · United States
External Links
PubMed source DOI: 10.1073/pnas.89.21.10321 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2