B-cell-independent sialylation of IgG.
IgG carrying terminal α2,6-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.
Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH 44106;
Mark B
MB
Jones
Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH 44106;
Douglas M
DM
Oswald
Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY 40536;
Smita
S
Joshi
Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY 40536;
Sidney W
SW
Whiteheart
Complex Carbohydrate Research Center, University of Georgia, Athens, GA 30602; Department of Biochemistry and Molecular Biology, University of Georgia, Athens, GA 30602.
Ron
R
Orlando
Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH 44106; brian.cobb@case.edu.
Brian A
BA
Cobb
D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism*; D001792:Blood Platelets / Q000378:metabolism; D007074:Immunoglobulin G / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D018345:Mice, Knockout; D010047:Ovalbumin / Q000276:immunology; D011134:Polysaccharides / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D012794:Sialic Acids / Q000378:metabolism*; D012799:Sialyltransferases / Q000235:genetics / Q000378:metabolism*; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase
D007074:Immunoglobulin G; D011134:Polysaccharides; D012794:Sialic Acids; D010047:Ovalbumin; D012799:Sialyltransferases; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase
B cell; IVIg; IgG; sialylation; sialyltransferase