Abstract
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 sialylationdependent 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.
Original language | English |
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Pages (from-to) | 7207-7212 |
Number of pages | 6 |
Journal | Proceedings of the National Academy of Sciences of the United States of America |
Volume | 113 |
Issue number | 26 |
DOIs | |
State | Published - Jun 28 2016 |
Bibliographical note
Funding Information:We thank Patrick Leahy, Jenifer Mikulan, Jenny L. Johnson, and Lori S. C. Kreisman for technical support and Richard D. Cummings and David F. Smith for coordinating the Consortium for Functional Glycomics (CFG) resources. This work was supported by NIH Grants OD004225 and GM082916 (to B.A.C.), AI007024 and AI114109 (to M.B.J.), AI089474 (to D.M.O.), GM062116 and GM098791 to the CFG, and HL056652 (to S.W.W.). Support also came from the Mizutani Foundation for Glycoscience (14-0023) and a Case Western Reserve University Clinical and Translational Science Collaborative Core Utilization Grant 06197 (to B.A.C.).
Keywords
- B cell
- IVIg
- IgG
- Sialylation
- Sialyltransferase
ASJC Scopus subject areas
- General