A chemokine-driven positive feedback loop organizes lymphoid follicles
A chemokine-driven positive feedback loop organizes lymphoid follicles
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DOI：
10.1038/35018581
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发表时间：
2000-07-20
期刊：
影响因子：
64.8
通讯作者：
Cyster, JG
中科院分区：
文献类型：
--
作者：
Ansel, KM;Ngo, VN;Cyster, JG
淋巴滤泡是淋巴器官中富含 B 细胞的区室，充当 B 细胞抗原相遇和分化的部位。 B 细胞迁移至脾滤泡需要 CXC 趋化因子受体 5 (CXCR5)(1)，但归巢至淋巴结中 B 细胞区域的要求仍有待确定。在这里，我们发现淋巴结包含两种类型的富含 B 细胞的区室：包含滤泡树突状细胞的滤泡和缺乏此类细胞的区域。使用基因靶向小鼠，我们确定 B 淋巴细胞趋化剂 (BLC/BCA1)(2,3) 及其受体 CXCR5 是 B 细胞归巢至淋巴结和脾脏滤泡所必需的。我们还发现 BLC 是大多数淋巴结和派尔氏淋巴结发育所必需的。除了介导化学吸引之外，BLC 还会诱导 B 细胞上调膜淋巴毒素 α1β2（一种促进滤泡树突细胞发育和 BLC 表达的细胞因子）(4,5)，从而建立一个可能对卵泡发育和体内平衡很重要的正反馈循环。在生发中心，反馈环路被忽略，B 细胞淋巴毒素 a1b2 的表达是由独立于 BLC 的机制诱导的。
Lymphoid follicles are B-cell-rich compartments of lymphoid organs that function as sites of B-cell antigen encounter and differentiation. CXC chemokine receptor-5 (CXCR5) is required for B-cell migration to splenic follicles(1), but the requirements for homing to B-cell areas in lymph nodes remain to be defined. Here we show that lymph nodes contain two types of B-cell-rich compartment: follicles containing follicular dendritic cells, and areas lacking such cells. Using gene-targeted mice, we establish that B-lymphocyte chemoattractant (BLC/BCA1)(2,3) and its receptor, CXCR5, are needed for B-cell homing to follicles in lymph nodes as well as in spleen. We also rnd that BLC is required for the development of most lymph nodes and Peyer's patches. In addition to mediating chemoattraction, BLC induces B cells to upregulate membrane lymphotoxin alpha 1 beta 2, a cytokine that promotes follicular dendritic cell development and BLC expression(4,5), establishing a positive feedback loop that is likely to be important in follicle development and homeostasis. In germinal centres the feedback loop is overridden, with B-cell lymphotoxin a1b2 expression being induced by a mechanism independent of BLC.