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亲和结合的CCL22促进了生殖中心的积极选择

Bo Liu^1,2,3, Yihan Lin^1,2,3, Jiacong Yan^1,2,3

¹Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing, China.

|February 18, 2021

概括

生殖中心B细胞使用化学因子CCL22和CCL17吸引毛囊辅助T细胞 (T_FH),确保高亲和度B细胞获得优先的T细胞帮助有效的抗体亲和度成熟.

科学领域:

免疫学
细胞生物学
分子生物学

背景情况:

通过具有较高亲和度B细胞受体的B细胞的阳性选择,抗体亲和度成熟发生在生殖中心 (GCs).
这种选择依赖于B细胞向毛囊辅助T细胞 (T_FH) 呈现更多的抗原并获得增强的T细胞帮助.
动态的GC环境对持续的B细胞-T_FH细胞相互作用提出了挑战,使得聚焦的T细胞帮助的机制不清楚.

研究的目的:

阐明T细胞帮助在生殖中心内累积聚焦于罕见的高亲和性B细胞克隆的机制.
研究化学因子在细胞间通信中介作用和T细胞在GC反应中的帮助.
了解B细胞亲和力如何影响T_FH细胞的吸引和随后的选择.

主要方法:

在GC B细胞和T_FH细胞中研究化学激素 (CCL22,CCL17) 和受体 (CCR4) 表达.
在B细胞中利用了CCL22和CCL17的基因切除,以评估它们对GC形成和亲和力成熟的影响.
评估了T_FH细胞调节对GCB细胞中的CCL22表达的影响.
在GC反应中比较了野生型B细胞与缺乏CCL22和CCL17的B细胞的竞争能力.

主要成果:

在CD40刺激时,GCB细胞调高CCL22和CCL17,通过CCR4吸引T_FH细胞.
在GCB细胞中较高的抗原结合 afinity 与增加的CCL22表达相关,突出显示这些细胞对T细胞的帮助.
T_FH细胞活动直接影响GCB细胞的CCL22表达,建立一个反电路.
切除CCL22和CCL17会损害B细胞亲和力成熟,并减少T细胞的帮助,阻碍GC参与和血细胞的发展.

结论:

一个含有CCL22/CCL17和CCR4的化学因子介导的电路通过优先地将T细胞的帮助指导到高亲和度B细胞来空间时间地调节GC阳性选择.
这种机制通过将最近的T细胞帮助与吸引进一步帮助的能力联系起来,确保了有效的抗体 afinity 成熟.
这项研究揭示了一种针对复杂的GC微环境中的免疫细胞相互作用的新原理.

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