Antigen-specific human monoclonal antibodies from mice engineered with human Ig heavy and light chain YACs

Nat Genet. 1994 May;7(1):13-21. doi: 10.1038/ng0594-13.

Abstract

We describe a strategy for producing human monoclonal antibodies in mice by introducing large segments of the human heavy and kappa light chain loci contained on yeast artificial chromosomes into the mouse germline. Such mice produce a diverse repertoire of human heavy and light chains, and upon immunization with tetanus toxin have been used to derive antigen-specific, fully human monoclonal antibodies. Breeding such animals with mice engineered by gene targeting to be deficient in mouse immunoglobulin (Ig) production has led to a mouse strain in which high levels of antibodies are produced, mostly comprised of both human heavy and light chains. These strains should provide insight into the adoptive human antibody response and permit the development of fully human monoclonal antibodies with therapeutic potential.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Factors
  • Amino Acid Sequence
  • Animals
  • Antibodies, Monoclonal / biosynthesis
  • Antibodies, Monoclonal / genetics
  • Antibodies, Monoclonal / immunology*
  • Antibody Formation
  • Base Sequence
  • Chromosomes, Artificial, Yeast*
  • Genes, Immunoglobulin*
  • Humans
  • Hybridomas / immunology
  • Immunoglobulin kappa-Chains / biosynthesis
  • Immunoglobulin kappa-Chains / genetics*
  • Immunoglobulin mu-Chains / biosynthesis
  • Immunoglobulin mu-Chains / genetics*
  • Mice
  • Mice, Transgenic / immunology*
  • Molecular Sequence Data
  • Recombinant Fusion Proteins / biosynthesis*
  • Recombinant Fusion Proteins / immunology
  • Sequence Alignment
  • Species Specificity
  • Tetanus Toxin / immunology
  • Tetanus Toxoid / biosynthesis
  • Tetanus Toxoid / immunology

Substances

  • Antibodies, Monoclonal
  • Immunoglobulin kappa-Chains
  • Immunoglobulin mu-Chains
  • Recombinant Fusion Proteins
  • Tetanus Toxin
  • Tetanus Toxoid