由旁观者B细胞和ICOS驱动的运动性控制的状T辅助细胞的招募
Heping Xu1, Xuanying Li, Dan Liu
1Tsinghua-Peking Center for Life Sciences, Laboratory of Dynamic Immunobiology, School of Medicine, Tsinghua University, Beijing 100084, China.
Nature
|April 27, 2013
概括
诱导性共刺激器 (ICOS) 控制T辅助细胞进入B细胞毛囊,独立于共刺激. 表达ICOSL的旁观者B细胞对于这种卵泡招募和生殖中心形成至关重要.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
背景情况:
- 生殖中心对适应性免疫非常重要,支持抗体亲和力成熟和记忆B细胞形成.
- 毛囊T助手 (Tfh) 细胞对于生殖中心的发展至关重要,促进B细胞的增殖和分化.
- 诱导性共刺激剂 (ICOS) 分子在Tfh细胞上高度表达,被认为对Tfh分化至关重要.
研究的目的:
- 研究ICOS在Tfh细胞功能和生殖中心形成中的精确作用.
- 确定ICOS影响Tfh细胞发育和局部化的机制.
- 阐明旁观者B细胞在Tfh细胞介导免疫反应中的贡献.
主要方法:
- 在小鼠中的遗传缺陷模型.
- 对T细胞迁移的动态体内成像.
- 对生殖中心形成和抗体反应的分析.
- 对Tfh细胞分化和局部化的评估.
主要成果:
- ICOS直接调节激活的T辅助细胞在B细胞毛囊中的毛囊招募.
- 这种招募独立于来自抗原呈现细胞的ICOS配体 (ICOSL) 同刺激.
- 由毛囊旁观者B细胞,而不是亲属B细胞表达ICOSL,对于Tfh细胞迁移和生殖中心形成至关重要.
- ICOS的参与促进了T细胞的协调迁移和T细胞/B细胞边界的伪肢形成.
结论:
- 在控制淋巴细胞组织内T辅助细胞的定位方面,ICOS具有协同刺激独立的功能.
- 旁观者B细胞在通过ICOSL参与支持Tfh细胞发育方面发挥着至关重要的,以前未被认可的作用.
- 这项研究揭示了T细胞迁移和定位的新机制,这对于有效的 humoral 免疫是必不可少的.
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