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与鼠类免疫系统出生后成熟相关的亚类特异性 IgG Fc 糖基化的变化。

Changes in subclass-specific IgG Fc glycosylation associated with the postnatal maturation of the murine immune system.

机构信息

Laboratory of Experimental Medicine, Hospital Alemán, Buenos Aires, Argentina.

National Scientific and Technical Research Council (CONICET), Buenos Aires, Argentina.

出版信息

Sci Rep. 2020 Sep 17;10(1):15243. doi: 10.1038/s41598-020-71899-7.

DOI:10.1038/s41598-020-71899-7
PMID:32943699
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7498460/
Abstract

Early postnatal life is characterized by a critical time period in which the developing neonatal immune system transitions from passive immunity, induced by protective maternal antibodies, to the competence of a fully functioning immune system. The inflammatory capability of both maternal and neonatal antibodies is governed by N-linked glycosylation of the Fc region, and though this has been examined extensively in adults, there is currently little information regarding antibody glycosylation patterns during early postnatal life. To characterize the murine IgG Fc glycosylation profile during early life, we used nano-LC-ESI-Qq-TOF mass spectrometry analysis to assess subclass specific Asn-297 glycosylation patterns in the serum of BALB/c mice from 5-60 days of age. From birth to adulthood, we observed a decline in proinflammatory Fc glycosylation in all IgG subclasses. This was shown by significantly reduced agalactosylated and monogalactosylated structures combined with increased sialylation after weaning at 45 and 60 days of age. This information indicates that the transition between neonatal life and adulthood in mice is accompanied by reduction of inflammatory IgG antibodies. Our study contributes to a growing body of literature indicating the importance of IgG Fc glycosylation and its association with inflammation during different life stages.

摘要

早期的产后生活以一个关键时期为特征,在此期间,发育中的新生儿免疫系统从由保护性母体抗体诱导的被动免疫转变为功能齐全的免疫系统的能力。母体和新生儿抗体的炎症能力受 Fc 区 N-连接糖基化的控制,尽管这在成人中已经得到了广泛的研究,但目前关于产后早期抗体糖基化模式的信息很少。为了描述早期生命中小鼠 IgG Fc 糖基化谱,我们使用纳升液相色谱-电喷雾-四极杆飞行时间质谱分析,评估了从 5 至 60 天龄 BALB/c 小鼠血清中 IgG 亚类的特异性 Asn-297 糖基化模式。从出生到成年,我们观察到所有 IgG 亚类中促炎 Fc 糖基化的下降。在 45 和 60 天龄断奶后,这种情况表现为半乳糖基化和单半乳糖基化结构明显减少,同时唾液酸化增加。这些信息表明,小鼠从新生儿期到成年期的过渡伴随着炎症性 IgG 抗体的减少。我们的研究为越来越多的文献提供了支持,这些文献表明 IgG Fc 糖基化及其与不同生命阶段炎症的关联的重要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae14/7498460/8a63e5c7957e/41598_2020_71899_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae14/7498460/632561f4ff0f/41598_2020_71899_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae14/7498460/3604681a4c36/41598_2020_71899_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae14/7498460/ec6a7d555bd0/41598_2020_71899_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae14/7498460/5e972c457a13/41598_2020_71899_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae14/7498460/8a63e5c7957e/41598_2020_71899_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae14/7498460/632561f4ff0f/41598_2020_71899_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae14/7498460/3604681a4c36/41598_2020_71899_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae14/7498460/ec6a7d555bd0/41598_2020_71899_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae14/7498460/5e972c457a13/41598_2020_71899_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae14/7498460/8a63e5c7957e/41598_2020_71899_Fig5_HTML.jpg

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本文引用的文献

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2
A synopsis of recent developments defining how N-glycosylation impacts immunoglobulin G structure and function.综述了近期关于 N-糖基化如何影响免疫球蛋白 G 结构和功能的研究进展。
Glycobiology. 2020 Mar 20;30(4):214-225. doi: 10.1093/glycob/cwz068.
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IgG Fc glycosylation as an axis of humoral immunity in childhood.
Adv Exp Med Biol. 2021;1325:341-373. doi: 10.1007/978-3-030-70115-4_17.
IgG Fc 糖基化作为儿童体液免疫的一个轴心。
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Cell. 2019 Jun 27;178(1):202-215.e14. doi: 10.1016/j.cell.2019.05.044. Epub 2019 Jun 13.
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