Galectin-9 bridges human B cells to vascular endothelium while programming regulatory pathways.
Galectin-9 bridges human B cells to vascular endothelium while programming regulatory pathways.
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Galectin-9在编程调节途径时将人B细胞桥接到血管内皮。
DOI：
10.1016/j.jaut.2020.102575
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发表时间：
2021-03
影响因子：
12.8
通讯作者：
Dimitroff CJ
中科院分区：
文献类型：
--
作者：
Chakraborty A;Staudinger C;King SL;Erickson FC;Lau LS;Bernasconi A;Luscinskas FW;Perlyn C;Dimitroff CJ
体液免疫依赖于循环幼稚B细胞从血液到外周淋巴结（LN）的有效募集和幼稚B细胞向高亲和力抗体（Ab）产生细胞的及时转变。然而，目前对LN中协调B细胞粘附、活化和分化的因子的理解是不完整的。对幼稚B细胞的先前研究揭示了与假定的免疫调节剂半乳糖凝集素（Gal）-9的显著强结合，其减弱BCR活化和信号传导，暗示Gal-9是B细胞生物学中的负调节剂。在这里，我们研究了半乳糖苷-9定位在人类扁桃体和淋巴结和出土的显着高表达的半乳糖苷-9高内皮和毛细血管后静脉。粘附分析显示，Gal-9可以将人循环和幼稚B细胞桥接至血管内皮细胞（EC），同时减缓跨内皮迁移。此外，Gal-9与幼稚B细胞的相互作用诱导与细胞信号传导和膜/细胞骨架动力学调节相关的基因家族的整体转录。信号淋巴细胞活化分子F7（SLAMF 7）是通过Gal-9结合升高的关键免疫调节剂之一，而细胞活化所需的SLAMF 7的胞质衔接子EAT-2被消除。Gal-9还激活促存活因子ERK的磷酸化。总之，这些数据表明Gal-9促进B细胞- EC相互作用，同时递送无反应性信号以控制B细胞反应性。
Humoral immunity is reliant on efficient recruitment of circulating naive B cells from blood into peripheral lymph nodes (LN) and timely transition of naive B cells to high affinity antibody (Ab)-producing cells. Current understanding of factor(s) coordinating B cell adhesion, activation and differentiation within LN, however, is incomplete. Prior studies on naïve B cells reveal remarkably strong binding to putative immunoregulator, galectin (Gal)-9, that attenuates BCR activation and signaling, implicating Gal-9 as a negative regulator in B cell biology. Here, we investigated Gal-9 localization in human tonsils and LNs and unearthed conspicuously high expression of Gal-9 on high endothelial and post-capillary venules. Adhesion analyses showed that Gal-9 can bridge human circulating and naïve B cells to vascular endothelial cells (EC), while decelerating transendothelial migration. Moreover, Gal-9 interactions with naïve B cells induced global transcription of gene families related to regulation of cell signaling and membrane/cytoskeletal dynamics. Signaling lymphocytic activation molecule F7 (SLAMF7) was among key immunoregulators elevated by Gal-9-binding, while SLAMF7’s cytosolic adapter EAT-2, which is required for cell activation, was eliminated. Gal-9 also activated phosphorylation of pro-survival factor, ERK. Together, these data suggest that Gal-9 promotes B cell – EC interactions while delivering anergic signals to control B cell reactivity.
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影响因子：
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