CXCL13 is an arrest chemokine for B cells in high endothelial venules
CXCL13 is an arrest chemokine for B cells in high endothelial venules
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DOI：
10.1182/blood-2005-01-0133
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发表时间：
2005-10-15
期刊：
影响因子：
20.3
通讯作者：
Miyasaka, M
中科院分区：
文献类型：
--
作者：
Kanemitsu, N;Ebisuno, Y;Miyasaka, M
趋化因子受体信号对淋巴细胞通过高内皮微静脉(HEV)是至关重要的，但HEV中表达的单个趋化因子的确切作用模式尚不清楚。在此，我们报道了CXCL13，在相当大比例的HEV中表达，在淋巴结(LNS)和Peyer斑块(PPS)中，作为一种B细胞的抑制趋化因子。对肠系膜LNS(MLN)的整体安装分析表明，与T细胞不同，B细胞与CXCL13(-/-)小鼠的HEV黏附能力很差，当CXCL13(-/-)HEV通过灌流添加到MLN中时，B细胞黏附得到显著恢复，就像我们之前在活体显微镜下观察到的PP HEV一样。在体外，CXCL13激活了B细胞中的小鸟苷三磷酸酶(GTPase)RAP1，证实了这一观察结果，RAPL效应分子RAPL的缺失导致抗剪切B细胞与细胞间黏附分子1(ICAM-1)的黏附显著减少。此外，CXCL13还通过激活α4整合素诱导B细胞与粘膜地址素细胞黏附分子1(MAdCAM-1)的黏附。这些数据证实CXCL13是HEV中B细胞的阻滞性趋化因子，表明CXCL13不仅在B细胞进入PPS中发挥重要作用，而且在MLN中也发挥重要作用。
Chemokine receptor signaling is critical for lymphocyte trafficking across high endothelial venules (HEVs), but the exact mode of action of individual chemokines expressed in the HEVs is unclear. Here we report that CXCL13, expressed in a substantial proportion of HEVs in both lymph nodes (LNs) and Peyer patches (PPs), serves as an arrest chemokine for B cells. Whole-mount analysis of mesenteric LNs (MLNs) showed that, unlike T cells, B cells adhere poorly to the HEVs of CXCL13(-/-) mice and that B-cell adhesion is substantially restored in CXCL13(-/-) HEVs when CXCL13 is added to the MLNs by superfusion, as we have previously observed in PP HEVs by intravital microscopy. In vitro, CXCL13 activated the small guanosine triphosphatase (GTPase) Rap1 in B cells, and corroborating this observation, a deficiency of RAPL, the Rap1 effector molecule, caused a significant reduction in shear-resistant B-cell adhesion to intercellular adhesion molecule 1 (ICAM-1). In addition, CXCL13 induced B-cell adhesion to mucosal addressin cell adhesion molecule 1 (MAdCAM-1) by activating alpha 4 integrin. These data identify CXCL13 as an arrest chemokine for B cells in HEVs and show that CXCL13 plays an important role in B-cell entry into not only PPs but also MLNs.