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

Abstract

Antibodies of human origin for blood typing are increasingly difficult to obtain, and, despite aggressive efforts, MoAbs with specificities to several blood group polymorphisms have eluded production. As an approach for the generation of MoAbs with defined specificities, the feasibility of immunizing mice that are transgenic for the target polymorphism, Fy(a)/Fy(b) of the Duffy blood group system, was tested with a source of the antithetical antigen. Nontransgenic mice were immunized with recombinant Fy(b), and transgenic mice expressing human Fy(b) were immunized with recombinant Fy(a). 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 polymorphism. However, immunization of the transgenic mice resulted in production of the first example of murine Fy(a) MoAb (MIMA-19). This antibody is being used to screen for Fy(a-) blood donors and has been evaluated by many laboratories in an international workshop. This approach provides an effective method for producing MoAbs with specificities to polymorphic epitopes. These MoAbs are needed in transfusion medicine to identify antigen-negative donors and to alleviate the critical shortage of blood bank typing reagents, which currently are available only from human-derived sources.