2 MECHANISMS FOR IGG UPTAKE IN CULTURED HUMAN TROPHOBLAST - EVIDENCE FOR A NOVEL HIGH-AFFINITY FC RECEPTOR

The mechanism of IgG transport by the placental trophoblast was examin ed by studying IgG uptake by purified trophoblast maintained in cultur e. This model retains the ability to bind and endocytose human IgG fro m human serum. Comparison of the relative IgG uptake by the trophoblas t among the four subclasses of both human and mouse IgG indicates that the trophoblast IgG receptor has different affinities from those desc ribed for the three known human Fc gamma receptors, FcR gamma I, FcR g amma II, and FcR gamma III. These results suggest the presence of a no vel trophoblast Fc gamma receptor. Although Fc gamma RIII has been rep orted to be present on trophoblasts, immunocytochemical studies failed to detect binding to the cell surface of antibody-specific for Fc gam ma RIII, 3G8 MAb. In addition, blocking studies with MAb, 3G8 did not interfere with IgG uptake. Scatchard analysis of human IgG uptake reve aled a biphasic curve consistent with two distinct mechanisms for the transport of IgG by the trophoblast. The first is a higher affinity sy stem (K-a = 1.7 x 10(7) M(-1), 1.7 X 10(4) binding sites/cell) which e xhibits IgG subclass and species specificity, and the second is a low affinity system (K-a = 6.9 X 10(3) M(-1), 7.5 x 10(7) binding sites/ce ll).