Submitted August 7, 2006
Accepted November 16, 2006
Mouse models of IgG- and IgM-mediated hemolysis
David Austin Schirmer, Shuh-Chyung Song, Jeffrey P Baliff, Stephanie O Harbers, Raphael A Clynes, Anna Krop-Watorek, Gregory R Halverson, Marcin Czerwinski, and Steven L Spitalnik*
Dept of Pathology, Columbia University, New York, NY, United States
Dept of Pathology & Laboratory Medicine, University of Rochester, New York, NY, United States
Dept of Microbiology, Columbia University, New York, NY, United States
Ludwik Hirszfeld Insititue of Immunology & Experimental Therapy, Wroclaw, Poland
Dept of Immunochemistry, New York Blood Center, New York, NY, United States
* Corresponding author; email: ss2479{at}columbia.edu.
Well-characterized mouse models of alloimmune antibody-mediated hemolysis would provide a valuable approach for gaining greater insight into the pathophysiology of hemolytic transfusion reactions. To this end, mouse red blood cells (mRBC) from human glycophorin A transgenic (hGPA-Tg) donor mice were transfused into non-Tg recipients that had been passively immunized with IgG or IgM hGPA-specific monoclonal antibodies (MAb). In this novel murine "blood group system," mRBC from hGPA-Tg mice are "antigen positive" and mRBC from non-Tg mice are "antigen negative." Passive immunization of non-Tg mice with the IgG1 10F7 and IgG3 NaM10-2H12 anti-hGPA Mab each induced rapid clearance of incompatible transfused hGPA-Tg-mRBC in a dose-response manner. Using various knockout (KO) mice as transfusion recipients, both the complement system and activating Fc
receptors were found to be important in the clearance of incompatible mRBC by each of these IgG Mab. In addition, the IgM E4 anti-hGPA Mab induced complement-dependent intravascular hemolysis of transfused incompatible hGPA-Tg-mRBC accompanied by gross hemoglobinuria. These initial studies validate the relevance of these new mouse models for addressing important questions in the field of transfusion medicine.
