Plasma ST6Gal1 is Dispensable for IgG Sialylation
The glycosylation of IgG has attracted increased attention due to the impact of N-glycan modifications at N297 on IgG function, acting primarily through modulation of Fc domain conformation and Fc{gamma} receptor binding affinities and signaling. However, the mechanisms regulating IgG glycosylation and especially 2,6-sialylation of its N-glycan remain poorly understood. We observed previously that IgG is normally sialylated in mice with B cells lacking the sialyltransferase ST6Gal1. This supported the hypothesis that IgG may be sialylated outside of B cells, perhaps through the action of hepatocyte-released plasma ST6Gal1. Here we demonstrate that this model is incorrect. Animals lacking hepatocyte expressed ST6Gal1 retain normal IgG 2,6-sialylation, despite the lack of detectable ST6Gal1 in plasma. Moreover, we confirmed that B cells were not a redundant source of IgG sialylation. Thus, while 2,6-sialylation is lacking in IgG from mice with germline ablation of ST6Gal1, IgG 2,6-sialylation is normal in mice lacking ST6Gal1 in either hepatocytes or B cells. These results indicate that IgG 2,6-sialylation arises after release from a B cell, but is not dependent on plasma-localized ST6Gal1 activity.