Evidence for the erythrocyte as the principal antigenic cell type that triggers primary IgM antibody responses to H-2D alloantigens.

Antigenic requirements for the induction of T cell-independent primary splenic IgM antibody responses (plaque-forming cell responses) to H-2Dd alloantigens were studied. Results show that some functional activity or structural property of the donor cells is required for immunogenicity, because antigens are not active in subcellular forms. An unexpected finding was that allogeneic red blood cells were exceptionally highly immunogenic, and any lymphoid tissues including purified macrophages and tumor cell lines that were not contaminated with red blood cells were virtually nonimmunogenic. The definite role of red blood cells in donor tissues as immunogens was confirmed by water or ammonium chloride treatment that abolished immunogenicity, as well as by phenotyping of the immunogenic cells with antisera. Thus immunogenic cells were positive for erythrocyte-specific and H-2D antigens and negative for Thy-1, Ig, and NK-1. The possible roles of erythrocytes in induction and regulation of transplantation immunity and in B cell activation in general are discussed.