Galectin-9 suppresses B cell receptor signaling and is regulated by I-branching of N-glycans.
Galectin-9 suppresses B cell receptor signaling and is regulated by I-branching of N-glycans.
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DOI：
10.1038/s41467-018-05770-9
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发表时间：
2018-08-17
影响因子：
16.6
通讯作者：
Dimitroff CJ
中科院分区：
文献类型：
--
作者：
Giovannone N;Liang J;Antonopoulos A;Geddes Sweeney J;King SL;Pochebit SM;Bhattacharyya N;Lee GS;Dell A;Widlund HR;Haslam SM;Dimitroff CJ
白细胞被一层不同种类的碳水化合物(多糖)所覆盖，这些碳水化合物调节免疫功能，部分是通过控制与糖结合蛋白(凝集素)的特定相互作用。虽然几乎所有的膜蛋白都含有葡聚糖，但大多数糖类在白细胞上的特性和功能仍未被研究。在这里，我们描述了人类扁桃体B细胞的N-糖链(N-糖链)。我们观察到幼稚和记忆B细胞表达一种N-糖链，与免疫调节凝集素Galectin-9(Gal-9)有很强的结合。相比之下，生发中心B细胞与Gal-9的结合急剧减少，这是由于在β1，6-N-乙酰氨基葡萄糖转移酶GCNT2的催化下，I-分支N-糖链的上调。在功能上，我们发现Gal-9是由幼稚的B细胞自身产生的，与CD45结合，通过Lyn-CD22-SHP-1依赖的机制抑制钙信号，并钝化B细胞的激活。因此，我们的发现表明，Gal-9本质上调节B细胞的激活，并可能在稳态和生发中心内差异地调节BCR信号。白细胞表面覆盖有多聚糖，通过与凝集素的相互作用来调节免疫功能。在这里，作者描述了人类扁桃体B细胞的N-糖链。他们报告说，Gal-9是B细胞激活的内在调节因子，由于I-分支糖链的表达，它可能在稳态和生发中心内对BCR信号进行差异调制。
Leukocytes are coated with a layer of heterogeneous carbohydrates (glycans) that modulate immune function, in part by governing specific interactions with glycan-binding proteins (lectins). Although nearly all membrane proteins bear glycans, the identity and function of most of these sugars on leukocytes remain unexplored. Here, we characterize the N-glycan repertoire (N-glycome) of human tonsillar B cells. We observe that naive and memory B cells express an N-glycan repertoire conferring strong binding to the immunoregulatory lectin galectin-9 (Gal-9). Germinal center B cells, by contrast, show sharply diminished binding to Gal-9 due to upregulation of I-branched N-glycans, catalyzed by the β1,6-N-acetylglucosaminyltransferase GCNT2. Functionally, we find that Gal-9 is autologously produced by naive B cells, binds CD45, suppresses calcium signaling via a Lyn-CD22-SHP-1 dependent mechanism, and blunts B cell activation. Thus, our findings suggest Gal-9 intrinsically regulates B cell activation and may differentially modulate BCR signaling at steady state and within germinal centers. Leukocytes are coated with glycans that modulate immune function through interactions with lectins. Here, the authors characterize the N-glycan repertoire of human tonsillar B cells. They report that Gal-9 is an intrinsic regulator of B cell activation that may differentially modulate BCR signaling at steady state and within germinal centers due to expression of I-branched glycans.
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DOI：
10.1084/jem.186.9.1575
发表时间：
1997-11-03
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Delibrias CC;Floettmann JE;Rowe M;Fearon DT
通讯作者：
Fearon DT
影响因子：
32.4
作者：
Cornall, RJ;Cyster, JG;Goodnow, CC
通讯作者：
Goodnow, CC
影响因子：
5.6
作者：
Henion, Timothy R.;Schwarting, Gerald A.
通讯作者：
Schwarting, Gerald A.
影响因子：
20.3
作者：
Clark, Mary C.;Pang, Mabel;Baum, Linda G.
通讯作者：
Baum, Linda G.
影响因子：
4.4
作者：
Boekers, Susanne;Urbat, Anne;Nitschke, Lars
通讯作者：
Nitschke, Lars