边缘区域B细胞以T细胞依赖的方式产生"自然"的体外保护性IgM抗体
James Harrison1, Stephen A Newland1, Wei Jiang1
1Department of Medicine, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK.
Cardiovascular research
|February 21, 2024
概括
边缘区域B细胞通过T毛囊辅助细胞调节动脉保护性IgM抗体,这是一项新发现,对动脉样硬化有治疗意义. 这项研究揭示了一种涉及IL18信号的Tfh依赖机制.
科学领域:
- 免疫学 免疫学 免疫学
- 心血管科学 心血管科学
背景情况:
- 动脉样硬化涉及适应性免疫反应.
- 毛囊T辅助细胞 (Tfh) 和边缘区域B细胞 (MZB) 起着复杂的作用.
- 诸如高脂肪/高胆固醇 (HF/HC) 饮食等饮食因素会影响免疫细胞的活动.
研究的目的:
- 研究Tfh细胞在动脉样硬化中的直接作用.
- 检查IL18在动脉样硬化期间Tfh细胞分化中的作用.
- 阐明MZB细胞,Tfh细胞和动脉样硬化中的抗体产生之间的关系.
主要方法:
- 产生了具有Tfh细胞,MZB细胞或Tfh细胞IL18信号传导的基因缺失的小鼠模型.
- 评估了动脉样硬化发展和抗体概况 (IgG,IgM) 与氧化特异性表位 (OSEs) 和抗醇 (PC) 相对应.
- 与人类样本中的抗体水平相关的MZB样细胞.
主要成果:
- 缺乏Tfh细胞的小鼠表现出动脉样硬化的增加.
- 由于Tfh细胞缺乏,降低了类切换IgG和动脉保护性IgM抗体.
- 缺少Tfh细胞导致MZB细胞积累,抗体分泌受损.
- IL18信号传递对于饮食引起的HF/HCTfh差异化至关重要.
结论:
- MZB细胞以Tfh-依赖的方式调节动脉保护性天然IgM抗体.
- 这种涉及IL18的Tfh依赖机制对动脉样硬化有显著的病理生理学影响.
- 研究结果表明,通过调节B细胞和Tfh细胞相互作用,可以为动脉样硬化治疗新的治疗点.
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