Naturally occurring human "antigalactosyl" IgG antibodies are heterophile antibodies recognizing blood-group-related substances

IgG autoantibodies in human serum bind selectively to a new antigen that appears on senescent erythrocytes, thereby initiating their removal from the circulation. We tested the hypothesis that these IgG molecules recognize terminal galactose residues, thought by some investigators to become exposed as cells age. Results revealed that human antibodies with an "antigalactosyl" specificity are heterophile antibodies directed against rabbit and not human red cells. This was demonstrated using hemagglutination assays and immunoblotting. Immunoblots performed with affinity purified antigalactosyl antibodies revealed binding of the antibodies to rabbit, but not human, erythrocyte membrane proteins. They have a broad range of specificities including anti-B, anti-I, and possibly anti-P1 and Pk. These heterophile antibodies are not involved in the physiological removal of senescent human RBC by macrophages as indicated by the data demonstrating that incubation of senescent red cells aged in situ with galactose prior to incubation with macrophages does not alter their phagocytosis. Senescent cell IgG does not have an antigalactosyl specificity because IgG eluted from senescent cells aged in situ does not bind to rabbit red cells that have exposed alpha-galactosyl moieties.