B-cell-independent sialylation of IgG
B-cell-independent sialylation of IgG
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DOI：
10.1073/pnas.1523968113
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发表时间：
2016-06-28
影响因子：
11.1
通讯作者：
Cobb, Brian A.
中科院分区：
文献类型：
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作者：
Jones, Mark B.;Oswald, Douglas M.;Cobb, Brian A.
携带末端α 2，6-连接的唾液酸的IgG通过唾液酸转移酶ST 6 Gal 1添加到Fc结构域内的保守N-聚糖上，解释了大剂量静脉注射IG（IVIg）在自身免疫中的抗炎作用。在此，小鼠中ST 6 Gal 1的B细胞特异性消融揭示了IgG唾液酸化可以独立于B细胞分泌途径发生在血流的细胞外环境中。我们还发现，分泌的ST 6 Gal 1是由肝中中央静脉内衬的细胞产生的，并且IgG唾液酸化是由血清定位的核苷酸糖供体CMP-唾液酸提供动力的，所述CMP-唾液酸至少部分来源于脱粒血小板。因此，抗体分泌细胞并不完全控制IgG的唾液酸化依赖性抗炎功能。相反，IgG唾液酸化可以由肝脏和血小板通过将酶和糖供体相应地释放到心血管循环中来调节。
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.