HIFI-[alpha] activation underlies a functional switch in the paradoxical role of Ezh2/PRC2 in breast cancer

IgG carrying terminal a2,6-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 c...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2016-06, Vol.113 (26), p.E3735
Main Authors: Mahara, Sylvia, Lee, Puay Leng, Feng, Min, Tergaonkar, Vinay, Chng, Wee Joo, Yu, Qiang
Format: Article
Language:English
Subjects:
Blood platelets
Immunity (Disease)
Immunoglobulins
Liver
Lymphocytes
Sugar
Online Access:Get full text
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Summary:IgG carrying terminal a2,6-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.
ISSN:0027-8424
1091-6490