Immunoglobulin G‐mediated regulation of the murine immune response to transfused red blood cells occurs in the absence of active immune suppression: implications for the mechanism of action of anti‐D in the prevention of haemolytic disease of the fetus and newborn?

Summary Anti‐D has been widely and effectively used in Rhesus blood group D negative mothers for the prevention of haemolytic disease of the fetus and newborn; its mechanism of action however, often referred to as antibody‐mediated immune suppression (AMIS), remains largely unresolved. We investigated, in a murine model, whether active immune suppression or clonal deletion mediated by anti‐red blood cell (RBC) immunoglobulin G (IgG) could explain the phenomenon of AMIS. Transfusion of IgG‐opsonized foreign RBCs (i.e. AMIS) strongly attenuated antibody responses compared to transfusion of untreated foreign RBCs. When the AMIS‐mice were subsequently transfused with untreated RBCs, no immune suppression was observed at 5 and 35 days after AMIS induction; in fact, the mice responded to retransfusion with untreated RBCs in a manner that was characteristic of a secondary immune response. When IgG‐opsonized RBCs were transfused concurrently with untreated RBCs, a dose‐dependent reduction of the antibody response was observed. This work suggests that the attenuation of the antibody responsiveness by anti‐RBC IgG is not associated with active immune suppression or clonal deletion at either the T‐cell or B‐cell level; rather, the effect appears more characteristic of B‐cell unresponsiveness to IgG‐opsonized RBCs. These results may have implications for the understanding of the mechanism of action of anti‐D in haemolytic disease of the fetus and newborn.