Mice are unsuitable for modelling ABO discordance despite strain-specific A cross-reactive natural IgM

ABO blood group antigens are immunodominant cell surface oligosaccharides. The function of the ABO system is clinically important in blood transfusion and solid organ transplantation but there is no small animal model of ABO discordance. The present study demonstrated A glycoconjugate-reactive IgM in the serum of CBA/Ca mice by enzyme-linked immunosorbent assay but showed with sugar blocking that the specificity of this IgM was different from that of human anti-A IgM. Furthermore, immunisation of CBA/Ca mice with the A antigen did not increase reactive IgM titre. In contrast, knock-out mice for the related carbohydrate antigen galactose(alpha1,3)galactose mounted a serum IgM response when immunised with the non-self galactose(alpha1,3)galactose antigen, which was shown to be T cell-dependent using a nude/knock-out animal. Reverse transcription-polymerase chain reaction identified transcripts for the enzyme likely to be responsible for the synthesis of the A antigen in organs from CBA/Ca mice although the A antigen was not detected in the same organs by immunohistochemistry. We conclude that CBA/Ca mice possess natural serum IgM with different characteristics to human anti-A IgM and that CBA/Ca mice may also express the A antigen. As a result, these mice are not suitable for use as a small animal model of ABO discordance.