A repertoire of monoclonal antibodies with human heavy chains from transgenic mice.

The introduction of human immunoglobulin gene segments in their unrearranged configuration into the germ line of mice might allow the production of a repertoire of human antibodies. Such transgenic mice could be used for the production of human monoclonal antibodies against human antigens. To test the feasibility of this approach, mice were created that carry a human heavy-chain minilocus comprising unrearranged immunoglobulin variable, diversity, and joining elements linked to a human mu-chain gene. The gene segments of this minilocus are rearranged in a large proportion of cells in thymus and spleen but not in nonlymphoid tissue. Some 4% of the B lymphocytes synthesize human mu chains resulting in a serum titer of about 50 micrograms of transgenic IgM antibody per ml. Hybridomas were established from the transgenic mice that stably secreted several micrograms of antibodies containing human mu heavy chains per milliliter.