Human antibodies are produced in transgenic chickens having functional
genetic components of the human immune system stably integrated in the
genome. Techniques are described to integrate unrearranged human heavy
and light chain immunoglobulin loci into the genome of the transgenic
chicken. The functional description of the endogenous immunoglobulin loci
yields an animal whose antibody repertoire in response to antigen is
fully human. In the preferred embodiment, the human immunoglobulin locus
is at least as large as the native human locus and exhibits functional
class switching to yield IgG isotype antibodies. In addition to
monoclonal antibodies secreted from immortalized B cell populations,
polyclonal antibodies may be obtained from eggs laid by the transgenic
chickens of the invention.