TRANSGENIC TRANSCHROMOSOMAL RODENTS FOR MAKING HUMAN ANTIBODIES

摘要

The present invention provides a transgenic nonhuman mammal, preferably a rodent, comprising two human immunoglobulin loci, wherein one of two said human immunoglobulin loci is a human heavy chain locus and the other locus is a human light chain locus; and wherein only one of said loci is of a transchromosome. In some transgenic nonhuman mammals, the endogenous mammalian heavy chain locus and at least one mammalian light chain locus are inactivated. In some such transgenic nonhuman mammals, the endogenous mammalian heavy chain locus and kappa light chain locus are inactivated. The present invention further provides methods of generating a plurality of B cells from a transgenic nonhuman mammal expressing human antibody sequences. Additional methods of the invention comprise fusing the plurality of B cells with immortalized cells to form hybridomas. The present invention also provides methods of generating a human sequence antibody from a transgenic nonhuman mammal.