Fc-Glycosylation of IgG1 is Modulated by B-cell Stimuli
Fc-Glycosylation of IgG1 is Modulated by B-cell Stimuli
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DOI：
10.1074/mcp.m110.004655
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发表时间：
2011-05-01
影响因子：
7
通讯作者：
Wuhrer, Manfred
中科院分区：
文献类型：
--
作者：
Wang, Jun;Balog, Crina I. A.;Wuhrer, Manfred
我们最近的研究表明，与总血清IgG1相比，针对被认为参与类风湿关节炎发病机制的抗原的IgG1在其fc尾部含有不同的聚糖片段。鉴于fc连接的n -聚糖在IgG的结构和生物活性中起着至关重要的作用，抗体的fc糖基化受到了广泛的关注。然而，到目前为止，关于影响这些碳水化合物结构组成的信号和因素对B淋巴细胞分泌的IgG的影响知之甚少。在这里，我们证明了“环境”因素，如全反式维甲酸（维生素a的天然代谢物），以及刺激先天免疫系统的因素（如CpG寡脱氧核苷酸，toll样受体9的配体）或来自适应性免疫系统的因素（如白细胞介素-21，一种t细胞衍生的细胞因子）都可以调节IgG1 fc糖基化。这些因素以不同的方式影响fc -聚糖谱。CpG寡脱氧核苷酸和白介素-21增加fc连接的半乳糖基化，降低分割n-乙酰氨基葡萄糖水平，而全反式维甲酸显著降低半乳糖基化和唾液基化水平。此外，这些作用似乎对分泌的IgG1是稳定和特异性的，因为在细胞聚糖池中没有观察到相应的聚糖的平行变化。有趣的是，已知影响b细胞生物学和抗体产生的其他几种细胞因子和分子对IgG1 fc偶联聚糖谱没有影响。总之，这些数据表明，B细胞在激活和分化过程中接受的不同刺激可以调节分泌的IgG1的fc连接糖基化，而不影响一般的细胞糖基化机制。因此，我们的研究进一步加深了我们对细胞水平上IgG1糖基化调控的理解。中国生物医学工程学报（自然科学版），2011,31(2):444 - 444。
We have recently shown that IgG1 directed against antigens thought to be involved in the pathogenesis of rheumatoid arthritis harbor different glycan moieties on their Fc-tail, as compared with total sera IgG1. Given the crucial roles of Fc-linked N-glycans for the structure and biological activity of IgG, Fc-glycosylation of antibodies is receiving considerable interest. However, so far little is known about the signals and factors that could influence the composition of these carbohydrate structures on secreted IgG produced by B lymphocytes. Here we show that both "environmental" factors, such as all-trans retinoic acid (a natural metabolite of vitamin A), as well as factors stimulating the innate immune system (i.e. CpG oligodeoxynucleotide, a ligand for toll-like receptor 9) or coming from the adaptive immune system (i.e. interleukin-21, a T-cell derived cytokine) can modulate IgG1 Fc-glycosylation. These factors affect Fc-glycan profiles in different ways. CpG oligodeoxynucleotide and interleukin-21 increase Fc-linked galactosylation and reduce bisecting N-acetylglucosamine levels, whereas all-trans retinoic acid significantly decreases galactosylation and sialylation levels. Moreover, these effects appeared to be stable and specific for secreted IgG1 as no parallel changes of the corresponding glycans in the cellular glycan pool were observed. Interestingly, several other cytokines and molecules known to affect B-cell biology and antibody production did not have an impact on IgG1 Fc-coupled glycan profiles. Together, these data indicate that different stimuli received by B cells during their activation and differentiation can modulate the Fc-linked glycosylation of secreted IgG1 without affecting the general cellular glycosylation machinery. Our study, therefore, furthers our understanding of the regulation of IgG1 glycosylation at the cellular level. Molecular & Cellular Proteomics 10: 10.1074/mcp.M110.004655, 1-12, 2011.