Lymph node B lymphocyte trafficking is constrained by anatomy and highly dependent upon chemoattractant desensitization
Lymph node B lymphocyte trafficking is constrained by anatomy and highly dependent upon chemoattractant desensitization
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DOI：
10.1182/blood-2011-06-364273
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发表时间：
2012-01-26
期刊：
影响因子：
20.3
通讯作者：
Kehrl, John H.
中科院分区：
文献类型：
--
作者：
Park, Chung;Hwang, Il-Young;Kehrl, John H.
B淋巴细胞通过淋巴结（LNs）的再循环需要跨越内皮屏障和化学吸引剂触发的细胞迁移。在这里，我们展示LN解剖和化学引诱剂受体信号如何组织B淋巴细胞LN运输。血源性B细胞主要利用CCR7信号粘附高内皮小静脉（HEVs）。新的B细胞迁移缓慢地穿过HEV小泡周围空间，然后定位在附近，避开滤泡。最终，新到达的B细胞进入卵泡的基底部分，逐渐填充。相比之下，新到达的活化B细胞迅速穿过hev并向淋巴结滤泡迁移。在LN驻留期间，循环B细胞重新获得了鞘氨醇-1磷酸受体1 （S1P1）受体，并显著降低了它们对趋化因子的敏感性。最终，B细胞通过进入皮质淋巴管或返回皮质旁索而离开LN滤泡。进入淋巴后，B细胞失去极性，下调其S1P1受体，随后强烈上调其对趋化因子的敏感性。这些结果在B细胞通过LNs的稳态运输模型中得到了总结。(血。2012;119 (4):978 - 989)
B lymphocyte recirculation through lymph nodes (LNs) requires crossing endothelial barriers and chemoattractant-triggered cell migration. Here we show how LN anatomy and chemoattractant receptor signaling organize B lymphocyte LN trafficking. Blood-borne B cells predominately used CCR7 signaling to adhere to high endothelial venules (HEVs). New B cell emigrants slowly transited the HEV perivenule space, and thereafter localized nearby, avoiding the follicle. Eventually, the newly arrived B cells entered the basal portion of the follicle gradually populating it. In contrast, newly arriving activated B cells rapidly crossed HEVs and migrated toward the lymph node follicle. During their LN residency, recirculating B cells reacquired their sphingosine-1 phospate receptor 1 (S1P1) receptors and markedly attenuated their sensitivity to chemokines. Eventually, the B cells exited the LN follicle by entering the cortical lymphatics or returning to the paracortical cords. Upon entering the lymph, the B cells lost their polarity, down-regulated their S1P1 receptors, and subsequently strongly up-regulated their sensitivity to chemokines. These results are summarized in a model of homeostatic trafficking of B cells through LNs. (Blood. 2012;119(4):978-989)