Immunization of transgenic mice for production of MoAbs directed at polymorphic blood group antigens

BACKGROUND: Antibodies of human origin for blood typing are increasingly di fficult to obtain, and, despite aggressive efforts, MoAbs with specificitie s to several blood group polymorphisms have eluded production. As an approa ch for the generation of MoAbs with defined specificities, the feasibility of immunizing mice that are transgenic for the target polymorphism, Fy(a)/F y(b) of the Duffy blood group system, was tested with a source of the antit hetical antigen. STUDY DESIGN AND METHODS: Nontransgenic mice were immunized with recombinan t Fy(b), and transgenic mice expressing human Fy(b) were immunized with rec ombinant Fy(a). RESULTS: Immunization of the nontransgenic mice resulted in the production of MoAbs to the Duffy protein, but not to the Fy(a)/Fy(b) blood group polym orphism. However, immunization of the transgenic mice resulted in productio n of the first example of murine Fy(a) MoAb (MIMA-19). This antibody is bei ng used to screen for Fy(a-) blood donors and has been evaluated by many la boratories in an international workshop. CONCLUSION: This approach provides an effective method for producing MoAbs with specificities to polymorphic epitopes. These MoAbs are needed in trans fusion medicine to identify antigen-negative donors and to alleviate the cr itical shortage of blood bank typing reagents, which currently are availabl e only from human-derived sources.