B-cell-independent sialylation of IgG

Mark B. Jones, Douglas M. Oswald, Smita Joshi, Sidney W. Whiteheart, Ron Orlando, Brian A. Cobb

Research output: Contribution to journalArticlepeer-review

78 Scopus citations

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 languageEnglish
Pages (from-to)7207-7212
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume113
Issue number26
DOIs
StatePublished - 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

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