Production of Antigen-Specific Human Monoclonal Antibodies: Comparison of Mice Carrying IgH/κ or IgH/κ/λ Transloci

Here we compare human monoclonal antibody (MAb) production from mouse strains that carry disruptions of their endogenous mouse IgH/Igκ loci and harbor human IgM + Igκ (BABκ) or human IgM + Igκ + Igλ transloci (BABκ,λ). We found that whereas both strains proved effective for the isolation of antigen-specific IgM antibodies, many of the IgM MAbs elicited from BABκ comprise human μ chains that are associated with mouse λ chains. In contrast, BABκ,λ mice gave rise to fully functional, polymeric human IgM antibodies comprising both human IgH and human IgL chains. Therefore, the inclusion of a human Igλ translocus (in addition to the human IgH + Igκ transloci) not only diminishes problems of endogenous mouse Igλ expression but also provides a strain of mice that yields fully human MAbs to a wide range of antigens, as witnessed by the isolation of MAbs to human blood cells, tumor cell lines, and an immunoglobulin idiotype.