B-cell-independent sialylation of IgG

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

doi:10.1073/pnas.1523968113

B-cell-independent sialylation of IgG

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

Molecular and Cellular Biochemistry

Research output: Contribution to journal › Article › peer-review

111 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 language	English
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	https://doi.org/10.1073/pnas.1523968113
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.).

Funding

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.).

Funders	Funder number
Consortium for Functional Glycomics
National Institutes of Health (NIH)	GM082916, AI089474, AI114109, GM062116, OD004225, HL056652, GM098791
National Institute of Allergy and Infectious Diseases	T32AI007024
Case Western Reserve University	06197
Mizutani Foundation for Glycoscience	14-0023

Keywords

B cell
IVIg
IgG
Sialylation
Sialyltransferase

ASJC Scopus subject areas

General

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10.1073/pnas.1523968113

Cite this

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title = "B-cell-independent sialylation of IgG",

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.",

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author = "Jones, \{Mark B.\} and Oswald, \{Douglas M.\} and Smita Joshi and Whiteheart, \{Sidney W.\} and Ron Orlando and Cobb, \{Brian A.\}",

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.).",

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AU - Oswald, Douglas M.

AU - Joshi, Smita

AU - Whiteheart, Sidney W.

AU - Orlando, Ron

AU - Cobb, Brian A.

N1 - 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.).

PY - 2016/6/28

Y1 - 2016/6/28

N2 - 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.

AB - 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.

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KW - Sialylation

KW - Sialyltransferase

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B-cell-independent sialylation of IgG

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

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