Logo of pnasPNASInfo for AuthorsSubscriptionsAboutThis Article
Proc Natl Acad Sci U S A. Nov 1984; 81(21): 6851–6855.
PMCID: PMC392030

Chimeric human antibody molecules: mouse antigen-binding domains with human constant region domains.

Abstract

We have created mouse-human antibody molecules of defined antigen-binding specificity by taking the variable region genes of a mouse antibody-producing myeloma cell line with known antigen-binding specificity and joining them to human immunoglobulin constant region genes using recombinant DNA techniques. Chimeric genes were constructed that utilized the rearranged and expressed antigen-binding variable region exons from the myeloma cell line S107, which produces an IgA (kappa) anti-phosphocholine antibody. The heavy chain variable region exon was joined to human IgG1 or IgG2 heavy chain constant region genes, and the light chain variable region exon from the same myeloma was joined to the human kappa light chain gene. These genes were transfected into mouse myeloma cell lines, generating transformed cells that produce chimeric mouse-human IgG (kappa) or IgG (kappa) anti-phosphocholine antibodies. The transformed cell lines remained tumorigenic in mice and the chimeric molecules were present in the ascitic fluids and sera of tumor-bearing mice.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.0M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Oi VT, Morrison SL, Herzenberg LA, Berg P. Immunoglobulin gene expression in transformed lymphoid cells. Proc Natl Acad Sci U S A. 1983 Feb;80(3):825–829. [PMC free article] [PubMed]
  • Gillies SD, Morrison SL, Oi VT, Tonegawa S. A tissue-specific transcription enhancer element is located in the major intron of a rearranged immunoglobulin heavy chain gene. Cell. 1983 Jul;33(3):717–728. [PubMed]
  • Ochi A, Hawley RG, Hawley T, Shulman MJ, Traunecker A, Köhler G, Hozumi N. Functional immunoglobulin M production after transfection of cloned immunoglobulin heavy and light chain genes into lymphoid cells. Proc Natl Acad Sci U S A. 1983 Oct;80(20):6351–6355. [PMC free article] [PubMed]
  • Kwan SP, Rudikoff S, Seidman JG, Leder P, Scharff MD. Nucleic acid and protein sequences of phosphocholine-binding light chains. J Exp Med. 1981 May 1;153(5):1366–1370. [PMC free article] [PubMed]
  • Clarke C, Berenson J, Goverman J, Boyer PD, Crews S, Siu G, Calame K. An immunoglobulin promoter region is unaltered by DNA rearrangement and somatic mutation during B-cell development. Nucleic Acids Res. 1982 Dec 11;10(23):7731–7749. [PMC free article] [PubMed]
  • Mulligan RC, Berg P. Expression of a bacterial gene in mammalian cells. Science. 1980 Sep 19;209(4463):1422–1427. [PubMed]
  • Mulligan RC, Berg P. Selection for animal cells that express the Escherichia coli gene coding for xanthine-guanine phosphoribosyltransferase. Proc Natl Acad Sci U S A. 1981 Apr;78(4):2072–2076. [PMC free article] [PubMed]
  • Sandri-Goldin RM, Goldin AL, Levine M, Glorioso JC. High-frequency transfer of cloned herpes simplex virus type 1 sequences to mammalian cells by protoplast fusion. Mol Cell Biol. 1981 Aug;1(8):743–752. [PMC free article] [PubMed]
  • Chu G, Sharp PA. SV40 DNA transfection of cells in suspension: analysis of efficiency of transcription and translation of T-antigen. Gene. 1981 Mar;13(2):197–202. [PubMed]
  • Oi VT, Herzenberg LA. Localization of murine Ig-1b and Ig-1a (IgG 2a) allotypic determinants detected with monoclonal antibodies. Mol Immunol. 1979 Dec;16(12):1005–1017. [PubMed]
  • Oi VT, Bryan VM, Herzenberg LA, Herzenberg LA. Lymphocyte membrane IgG and secreted IgG are structurally and allotypically distinct. J Exp Med. 1980 May 1;151(5):1260–1274. [PMC free article] [PubMed]
  • O'Farrell PZ, Goodman HM, O'Farrell PH. High resolution two-dimensional electrophoresis of basic as well as acidic proteins. Cell. 1977 Dec;12(4):1133–1141. [PubMed]
  • Nose M, Wigzell H. Biological significance of carbohydrate chains on monoclonal antibodies. Proc Natl Acad Sci U S A. 1983 Nov;80(21):6632–6636. [PMC free article] [PubMed]
  • Miller RA, Levy R. Response of cutaneous T cell lymphoma to therapy with hybridoma monoclonal antibody. Lancet. 1981 Aug 1;2(8240):226–230. [PubMed]
  • Boss MA, Kenten JH, Wood CR, Emtage JS. Assembly of functional antibodies from immunoglobulin heavy and light chains synthesised in E. coli. Nucleic Acids Res. 1984 May 11;12(9):3791–3806. [PMC free article] [PubMed]
  • Morrison SL, Oi VT. Transfer and expression of immunoglobulin genes. Annu Rev Immunol. 1984;2:239–256. [PubMed]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

  • Cited in Books
    Cited in Books
    PubMed Central articles cited in books
  • Compound
    Compound
    PubChem Compound links
  • MedGen
    MedGen
    Related information in MedGen
  • PubMed
    PubMed
    PubMed citations for these articles
  • Substance
    Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...