期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 113, 期 26, 页码 7207-7212出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1523968113
关键词
IgG; sialylation; sialyltransferase; B cell; IVIg
资金
- NIH [OD004225, GM082916, AI007024, AI114109, AI089474, GM062116, GM098791, HL056652]
- Mizutani Foundation for Glycoscience [14-0023]
- Case Western Reserve University Clinical & Translational Science Collaborative Core Utilization Grant [06197]
IgG carrying terminal alpha 2,6-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.
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