Platelet-localized ST6Gal1 does not impact IgG sialylation.
Platelet-localized ST6Gal1 does not impact IgG sialylation.
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血小板定位的 ST6Gal1 不会影响 IgG 唾液酸化。
DOI：
10.1093/glycob/cwad052
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发表时间：
2023
期刊：
影响因子：
4.3
通讯作者：
Cobb,BrianA
中科院分区：
文献类型：
--
作者：
Glendenning,LeandreM;Zhou,JulieY;Kukan,EmilyN;Gao,Chao;Cummings,RichardD;Joshi,Smita;Whiteheart,SidneyW;Cobb,BrianA
IgG 抗体类型构成体液免疫反应的重要基础，提供针对病原体和自身免疫的相互保护。 IgG 功能由 IgG 亚类（由重链定义）以及 N297（Fc 结构域内 N-糖基化的保守位点）处的聚糖组成决定。例如，核心岩藻糖的缺乏会促进抗体依赖性细胞毒性的增加，而 ST6Gal1 酶引起的 α2,6 连接唾液酸化有助于驱动免疫静止。尽管这些碳水化合物具有免疫学意义，但人们对 IgG 聚糖组成如何调节知之甚少。我们之前报道过 ST6Gal1 缺陷 B 细胞的小鼠的 IgG 唾液酸化未改变。同样，肝细胞释放到血浆中的 ST6Gal1 不会显着影响整体 IgG 唾液酸化。由于 IgG 和 ST6Gal1 已被独立证明存在于血小板颗粒中，因此血小板颗粒有可能作为 IgG 唾液酸化的 B 细胞外源位点。为了解决这一假设，我们使用血小板因子 4 (Pf4)-Cre 小鼠单独删除巨核细胞和血小板中的 ST6Gal1，或与白蛋白-Cre 小鼠组合，将其从肝细胞和血浆中删除。产生的小鼠品系是可行的并且没有明显的病理表型。我们还发现，尽管 ST6Gal1 被靶向消除，但 IgG 唾液酸化没有明显变化。结合我们之前的发现，我们可以得出结论，在小鼠中，B 细胞、血浆和血小板在稳态 IgG 唾液酸化中都没有发挥重要作用。
The IgG antibody class forms an important basis of the humoral immune response, conferring reciprocal protection from both pathogens and autoimmunity. IgG function is determined by the IgG subclass, as defined by the heavy chain, as well as the glycan composition at N297, the conserved site of N-glycosylation within the Fc domain. For example, lack of core fucose promotes increased antibody-dependent cellular cytotoxicity, whereas α2,6-linked sialylation by the enzyme ST6Gal1 helps to drive immune quiescence. Despite the immunological significance of these carbohydrates, little is known about how IgG glycan composition is regulated. We previously reported that mice with ST6Gal1-deficient B cells have unaltered IgG sialylation. Likewise, ST6Gal1 released into the plasma by hepatocytes does not significantly impact overall IgG sialylation. Since IgG and ST6Gal1 have independently been shown to exist in platelet granules, it was possible that platelet granules could serve as a B cell-extrinsic site for IgG sialylation. To address this hypothesis, we used a platelet factor 4 (Pf4)-Cre mouse to delete ST6Gal1 in megakaryocytes and platelets alone or in combination with an albumin-Cre mouse to also remove it from hepatocytes and the plasma. The resulting mouse strains were viable and had no overt pathological phenotype. We also found that despite targeted ablation of ST6Gal1, no change in IgG sialylation was apparent. Together with our prior findings, we can conclude that in mice, neither B cells, the plasma, nor platelets have a substantial role in homeostatic IgG sialylation.