Mechanism of anti-D-mediated immune suppression – a paradox awaiting resolution?

During pregnancy, women can be immunized by fetal red blood cells (RBCs) of an incompatible blood group. Subsequent transplacental passage of the antibodies can result in fetal morbidity or mortality due to RBC destruction. The administration of anti-D antibodies to D− women after delivery of a D+ infant, and subsequent prevention of Rhesus (Rh) D haemolytic disease of the fetus and newborn, is the most successful clinical use of antibody-mediated immune suppression. The passive IgG anti-D might prevent immunization to D+ RBCs by an IgG Fcγ receptor (Fcγ R)-dependent mechanism such as crosslinking the D-specific B-cell receptor and inhibitory FcγRIIb. However, recent murine studies demonstrate that the suppressive effects of antibodies to heterologous RBCs can be Fcγ R-independent, suggesting other mechanisms might contribute.