A novel Fc gamma R-defined, IgG-containing organelle in placental endothelium

Abstract

Placental transfer of IgG from maternal circulation to that of the fetus is crucial for fetal and newborn immunity. This process requires that IgG broach two cellular layers of the placenta. IgG transport across the first layer, the syncytiotrophoblast, is almost certainly mediated by the MHC-related FcR for IgG, FcRn. The second layer, the villus endothelium, was until recently thought to allow IgG movement nonspecifically by constitutive transcytosis in caveolae. However, we recently showed that villus endothelium expressed a separate FcR for IgG, the inhibitory motif-bearing Fc gammaRIIb2 seen most notably on macrophages and as a minor fraction of the Fc gammaRIIb expressed on B cells. Now, by quantitative microscopy, we find Fc gammaRIIb2 to be expressed abundantly in an unidentifiable and likely novel organelle of the villus endothelium, unassociated with caveolae. About half of these Fc gammaRIIb2 organelles contain IgG; the remainder lack IgG. The majority fraction (approximately 80%) of IgG-containing organelles is associated with Fc gammaRIIb. No IgG-containing organelles are associated with caveolin. These findings are compatible with Fc gammaRIIb-mediated transfer of IgG across the villus endothelium, independent of caveolae.