A transgenic model of autoimmune hemolytic anemia

doi:10.1084/jem.175.1.71

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A transgenic model of autoimmune hemolytic anemia

M Okamoto, M Murakami, A Shimizu, S Ozaki, T Tsubata, S Kumagai and T Honjo
Department of Medical Chemistry, Faculty of Medicine, Kyoto University, Japan.

We made double transgenic mice bearing immunoglobulin heavy and light chain genes encoding an autoantibody against the mouse erythrocyte by the cross of C57BL/6 mice carrying the transgene for each chain of the immunoglobulin. Although no obvious disorders were found in the single- chain transgenic mice, severely anemic symptoms were found in some of the double transgenic mice, in which most B cells express, at least on their surface, the autoantibody reactive to self-antigens on the erythrocyte. Individual double-transgenic mice showed a wide variation of phenotypes between severe anemia and no symptoms. Both deletion and anergy of autoreactive B cells were seen in each individual mouse, but their relative contribution to self-tolerance was variable and not directly related to the severity of anemia or the amount of the autoantibody produced. This transgenic system provides a good autoimmune disease model for exploring its onset mechanism, and means of its treatment and prevention.
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