On the mechanism of tolerance to the Rh D antigen mediated by passive anti-D (Rh D prophylaxis)

Abstract

Anti-D prophylaxis is the most successful clinical application of antibody-mediated immune suppression. Passive IgG anti-D is given to Rh D-negative women to prevent immunisation to foetal Rh D-positive red blood cells (RBC) and subsequent haemolytic disease of the newborn. Despite its widespread use and efficacy, the mechanism of action of this therapy is unproven. The known facts about the antigen, antibody response, dose of anti-D, RBC clearance and effects of the passive anti-D on subsequent primary and secondary immune responses are discussed in relation to recent information on ways by which immune responses may be suppressed. Most Rh D antigen sites on RBC are not bound by passive anti-D, and thus epitope masking (which may occur in experimental murine models using xenogeneic RBC) is not the reason why anti-D responses are prevented by administration of prophylactic anti-D. It is hypothesised that although clearance and destruction of the antigenic RBC may be a contributing factor in preventing immunisation, down-regulation of antigen-specific B cells through co-ligation of B cell receptors and inhibitory IgG Fc receptors must also occur.