Balanced expression of CXCR5 and CCR7 on follicular T helper cells determines their transient positioning to lymph node follicles and is essential for efficient B-cell help
Balanced expression of CXCR5 and CCR7 on follicular T helper cells determines their transient positioning to lymph node follicles and is essential for efficient B-cell help
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DOI：
10.1182/blood-2004-11-4494
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发表时间：
2005-09-15
期刊：
影响因子：
20.3
通讯作者：
Förster, R
中科院分区：
文献类型：
--
作者：
Hardtke, S;Ohl, L;Förster, R
对T依赖性抗原的高亲和力抗体的产生需要B细胞和表达对相同抗原特异性的受体的T辅助细胞的相互作用。虽然已经阐明了几种调节淋巴器官内B细胞运输的机制，但对引导CD4（+）滤泡T辅助细胞的小亚群进入B细胞滤泡的分子线索知之甚少。使用小鼠转基因T细胞的过继转移，我们证明抗原诱导的激活会导致T细胞在T细胞区域或B细胞滤泡中的微调定位。我们表明，CXCR5的表达是T细胞进入B细胞卵泡所不可或缺的，而CCR7的表达提供了一个抵消信号，以保持活化的T细胞在T细胞区。尽管在抗原攻击后，只有少数T细胞从外周淋巴结的T细胞区域暂时迁移到B细胞滤泡，但这一步骤对于提供B细胞有效产生抗体所需的帮助是必不可少的。因此，我们证明了CCR7和CXCR5的平衡表达决定了滤泡性T辅助细胞的定位和正常功能。
The production of high-affinity antibodies to T-dependent antigens requires the interaction of B cells and T helper cells expressing receptors specific for the same antigen. Although several mechanisms have been elucidated that regulate B-cell trafficking within lymphoid organs, less is known about molecular cues that guide the small subpopulation of CD4(+) follicular T helper cells to B-cell follicles. Using adoptive transfer of transgenic T cells in mice, we demonstrate that antigen-induced activation leads to a finely tuned positioning of T cells either to the T-cell area or the B-cell follicle. We show that expression of CXCR5 is indispensable for T cells to enter B-cell follicles, whereas expression of CCR7 provides a counteracting signal to retain activated T cells in the T-cell area. Although only few T cells transiently migrate from the T-cell area to the B-cell follicle of peripheral lymph nodes following antigenic challenge, this step is essential to provide the help B cells require to produce antibodies efficiently. Thus, we demonstrate that the balanced expression of CCR7 and CXCR5 determines the positioning and proper function of follicular T helper cells.