Generation of a mouse strain that produces immunoglobulin kappa chains with human constant regions

Science. 1993 Nov 19;262(5137):1271-4. doi: 10.1126/science.8235658.

Abstract

Humanized antibodies are highly efficient as immunotherapeutic reagents and have many advantages over rodent antibodies. A mouse strain was generated by gene targeting to replace the mouse kappa light chain constant (C) region gene with the human C kappa gene. Mice homozygous for the replacement mutation (C kappa R) produced normal concentrations of serum antibodies, most of which carry chimeric kappa light chains, and mounted normal immune responses to hapten-protein conjugates. This technology provides a feasible option for the generation of high-affinity humanized antibodies by means of the powerful somatic hypermutation-selection mechanism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • B-Lymphocytes / immunology*
  • Base Sequence
  • Gene Rearrangement
  • Genes, Immunoglobulin*
  • Humans
  • Immunoglobulin Constant Regions / biosynthesis*
  • Immunoglobulin Constant Regions / genetics
  • Immunoglobulin Isotypes / biosynthesis
  • Immunoglobulin kappa-Chains / biosynthesis*
  • Immunoglobulin kappa-Chains / genetics
  • Mice
  • Mice, Transgenic
  • Molecular Sequence Data
  • Mutation
  • Polymerase Chain Reaction
  • Recombinant Fusion Proteins / biosynthesis
  • Stem Cells
  • Transfection

Substances

  • Immunoglobulin Constant Regions
  • Immunoglobulin Isotypes
  • Immunoglobulin kappa-Chains
  • Recombinant Fusion Proteins