biostudies-literatureJones MBNIAID NIH HHSNHLBI NIH HHSNIGMS NIH HHSNIH HHS7207-12https://www.ebi.ac.uk/biostudies/studies/S-EPMC4932940biostudies-literatureUnknown113(26)IgG carrying terminal ?2,6-linked sialic acids added to conserved N-glycans within the Fc domain by the sialyltransferase ST6Gal1 accounts for the anti-inflammatory effects of large-dose i.v. Ig (IVIg) in autoimmunity. Here, B-cell-specific ablation of ST6Gal1 in mice revealed that IgG sialylation can occur in the extracellular environment of the bloodstream independently of the B-cell secretory pathway. We also discovered that secreted ST6Gal1 is produced by cells lining central veins in the liver and that IgG sialylation is powered by serum-localized nucleotide sugar donor CMP-sialic acid that is at least partially derived from degranulating platelets. Thus, antibody-secreting cells do not exclusively control the sialylation-dependent anti-inflammatory function of IgG. Rather, IgG sialylation can be regulated by the liver and platelets through the corresponding release of enzyme and sugar donor into the cardiovascular circulation.Proceedings of the National Academy of Sciences of the United States of AmericaB-cell-independent sialylation of IgG.PMC4932940R01 HL056652R24 GM098791U54 GM062116DP2 OD004225T32 AI007024R01 GM082916F32 AI114109T32 AI089474Oswald DMOrlando RJones MBJoshi SCobb BAWhiteheart SWfalseB-cell-independent sialylation of IgG.IgG carrying terminal ?2,6-linked sialic acids added to conserved N-glycans within the Fc domain by the sialyltransferase ST6Gal1 accounts for the anti-inflammatory effects of large-dose i.v. Ig (IVIg) in autoimmunity. Here, B-cell-specific ablation of ST6Gal1 in mice revealed that IgG sialylation can occur in the extracellular environment of the bloodstream independently of the B-cell secretory pathway. We also discovered that secreted ST6Gal1 is produced by cells lining central veins in the liver and that IgG sialylation is powered by serum-localized nucleotide sugar donor CMP-sialic acid that is at least partially derived from degranulating platelets. Thus, antibody-secreting cells do not exclusively control the sialylation-dependent anti-inflammatory function of IgG. Rather, IgG sialylation can be regulated by the liver and platelets through the corresponding release of enzyme and sugar donor into the cardiovascular circulation.2016-01-01T00:00:00Z2016 Jun2020-10-09T07:31:23Z2019-03-27T02:17:35ZS-EPMC49329402730303110.1073/pnas.1523968113