ST6Gal1 in plasma is dispensable for IgG sialylation

The glycosylation of immunoglobulin G (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 alpha 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 alpha 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 alpha 2,6-sialylation is lacking in IgG from mice with germline ablation of ST6Gal1, IgG alpha 2,6-sialylation is normal in mice lacking ST6Gal1 in either hepatocytes or B cells. These results indicate that IgG alpha 2,6-sialylation arises after release from a B cell but is not dependent on plasma-localized ST6Gal1 activity.

Automated summary

The glycosylation of IgG is important for its function, but the mechanisms and factors involved are not well understood. This study suggests that alpha 2,6-sialylation of IgG occurs after release from B cells and is not dependent on plasma-localized ST6Gal1 activity.