Human placental Fc gamma-binding proteins in the maternofetal transfer of IgG.

Annexin II, a member of the annexin family of Ca2+ and phospholipid binding proteins, is present in human placenta. Placental annexin II has low affinity FcR activity, and is present as a heterotetramere on syncytiotrophoblast apical cell membrane extracellular surface. In addition to annexin II, transmembraneous leukocyte FcRIII is present on syncytiotrophoblast apical membrane. Either one, or both molecules may mediate the binding of IgG and thereby facilitate its transport through the syncytiotrophoblast layer. However, the presence of other maternal plasma proteins in syncytiotrophoblasts that are not transported to the human fetus is suggestive of nonspecific fluid phase endocytosis. The MHC class I like FcR, similar to the receptor found in neonatal rodent intestine, FcRn, is present intracellularly in human syncytiotrophoblasts, as is its light chain beta 2-microglobulin. The hFcRn is not detected on the apical plasma membrane. The placental hFcRn co-localizes with IgG in syncytiotrophoblast granules. It is likely that hFcRn binds and transcytoses IgG through the syncytiotrophoblast. Protected transfer of IgG may occur within syncytiotrophoblast endocytotic vesicles prior to release in the villous stroma and subsequent translocation into the lumen of fetal stem vessels by uptake and transport in endothelial caveolae.