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

In primates, prenatal transfer of IgG from mother to offspring occurs predo minantly across the placenta. Although a number of Fc gamma-receptors and I gG binding proteins have been detected in human placental tissue, an involv ement of any of these receptors in IgG transport across the syncytiotrophob last remains to be demonstrated. Therefore, we investigated the mechanism o f IgG transcytosis in trophoblast-derived BeWo cells. BeWo cells were not o nly found to express the MHC dass I-related IgG Fc receptor, human FcRn, bu t also specifically bound fluorescein isothiocyanate (FITC)-labeled human I gG (FITC-hIgG) at the apical surface at mildly acidic pH. The cells prefere ntially transcytosed FITC-hIgG from the apical to the basolateral side when compared to the fluid-phase marker FITC-dextran and to FITC-hIgG transcyto sis in the opposite direction. However, endocytosis of FITC-hIgG at the api cal plasma membrane at physiological pH required the continuous presence of FITC-hIgG at concentrations similar to those present in the maternal circu lation. These results suggest a mechanism by which IgG is internalized by B eWo cells via fluid-phase endocytosis. Tight binding of IgG to hFcRn may th en occur in acidic endosomes, followed by selective sorting into the transc ytotic pathway. Thus, the main function of this receptor is to prevent entr y of IgG into the degradative pathway in lysosomes.