GENERATION OF A MOUSE STRAIN THAT PRODUCES IMMUNOGLOBULIN-KAPPA CHAINS WITH HUMAN CONSTANT REGIONS

Humanized antibodies are highly efficient as immunotherapeutic reagent s and have many advantages over rodent antibodies. A mouse strain was generated by gene targeting to replace the mouse kappa light chain con stant (C) region gene with the human C(kappa) gene. Mice homozygous fo r 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-affi nity humanized antibodies by means of the powerful somatic hypermutati on-selection mechanism.