Endothelial cells sialylate IgG within the FcRn-mediated recycling pathway

IgG is a key to adaptive immunity and a critical platform for drug design. Sialic acid on the conserved glycan within the Fc domain is believed to promote anti-inflammatory IgG function; however, regulation of sialylation remains poorly defined. We previously showed that IgG sialylation is primarily mediated by B cell-extrinsic processes in mice. Here, we found that IgG sialylation occurs in the subcellular compartments of the FcRn-mediated IgG recycling pathway of endothelial cells. This process is down-regulated by inflammatory signals and up-regulated during gestation, providing mechanistic insight into the epidemiology associating IgG glycosylation, pregnancy and inflammatory disease. These findings demonstrate that plasma-localized IgG glycosylation is dynamically altered by the endothelium, revealing a potential mechanism through which the function of all endogenous and administered IgG and Fc-containing pharmaceuticals could be altered.