A Major Role of Class I Fcγ Receptors in Immunoglobulin G Anti-D--Mediated Red Blood Cell Destruction by Fetal Mononuclear Phagocytes

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Abstract
Objective: To examine Fcγ receptor (FcγR) classes that direct immunoglobulin (Ig) G anti-D—mediated red blood cell interaction with fetal mononuclear phagocytes. Methods: Mononuclear phagocytes isolated from fetal blood and spleen at 20–35 and 12–15 weeks' gestation, respectively, were tested in a modified mononuclear phagocytosis assay against IgG anti-D—coated red blood cells in the absence and presence of FcyR class-specific monoclonal antibodies as inhibitors. Monocytes from cord and adult blood served as controls. Results: In the absence of any inhibitor, attachment and phagocytosis indices of fetal monocytes were similar to those of their newborn and adult counterparts but markedly less than those of mononuclear phagocytes from fetal spleen. Blockade of the high-affinity FcγRI caused a profound (more than 93%) reduction in red blood cell attachment and phagocytosis indices of fetal as well as newborn and adult monocytes. It also brought about a marked decrease in the attachment and phagocytosis indices of mononuclear phagocytes from fetal spleens (64 and 81%, respectively). With fetal spleen mononuclear phagocytes, anti-FcγRII lacked any significant effect on their interaction with red blood cells, whereas anti-FcγRIII caused a significant (43%) inhibition of their phagocytosis. Conclusion: Immunoglobulin G anti-D—mediated attachment to and phagocytosis by fetal mononuclear phagocytes of red blood cells is well developed early during the second trimester. High-affinity FcγRI plays a major role in the effector function of circulating monocytes and splenic mononuclear phagocytes, whereas FcγRIII, expressed strongly on the latter effectors, participates in target ingestion.

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