IgG transport across trophoblast-derived BeWo cells: a model system to study IgG transport in the placenta

Abstract

In primates, prenatal transfer of IgG from mother to offspring occurs predominantly across the placenta. Although a number of Fcγ-receptors and IgG binding proteins have been detected in human placental tissue, an involvement of any of these receptors in IgG transport across the syncytiotrophoblast remains to be demonstrated. Therefore, we investigated the mechanism of IgG transcytosis in trophoblast-derived BeWo cells. BeWo cells were not only found to express the MHC class I-related IgG Fc receptor, human FcRn, but also specifically bound fluorescein isothiocyanate (FITC)-labeled human IgG (FITC-hIgG) at the apical surface at mildly acidic pH. The cells preferentially transcytosed FITC-hIgG from the apical to the basolateral side when compared to the fluid-phase marker FITC-dextran and to FITC-hIgG transcytosis in the opposite direction. However, endocytosis of FITC-hIgG at the apical plasma membrane at physiological pH required the continuous presence of FITC-hIgG at concentrations similar to those present in the maternal circulation. These results suggest a mechanism by which IgG is internalized by BeWo cells via fluid-phase endocytosis. Tight binding of IgG to hFcRn may then occur in acidic endosomes, followed by selective sorting into the transcytotic pathway. Thus, the main function of this receptor is to prevent entry of IgG into the degradative pathway in lysosomes.