生殖中心低氧和通过低氧反应系统调节抗体质量
Sung Hoon Cho1, Ariel L Raybuck1, Kristy Stengel2
1Department of Pathology, Microbiology and Immunology, Vanderbilt University, Nashville, Tennessee 37232, USA.
Nature
|August 9, 2016
概括
在生殖中心 (GCs) 的低氧水平会损害B细胞功能,影响抗体的产生和记忆细胞的形成. 这突显了氧气感应在调节体内免疫力和疫苗反应中的作用.
科学领域:
- 免疫学
- 细胞生理学
- 分子生物学
背景情况:
- 生殖中心 (GC) 对体内免疫和疫苗有效性至关重要,涉及B细胞增殖,抗体亲和力成熟和记忆生成.
- 虽然细胞因子环境是已知的调节者,但代谢编程和细胞微环境正成为免疫反应的关键调节者.
研究的目的:
- 研究氧气紧张在小鼠生殖中心B细胞的生理和功能调节中的作用.
- 阐明缺氧影响B细胞功能,抗体类别切换和记忆发展的机制.
主要方法:
- 在小鼠GC光线区域中分析氧气水平.
- 研究了缺氧对B细胞增殖,死亡和抗体类别切换的影响.
- 利用B细胞特异性的佩尔-兰多瘤抑制蛋白 (pVHL) 诱导低氧诱导因子 (HIF) 稳定.
- 研究了HIF和mTOR复合体1 (mTORC1) 在B细胞代谢和功能中的作用.
主要成果:
- GC光区表现出缺氧状况,这会对B细胞生理产生负面影响,减少细胞增殖和增加细胞死亡.
- 低氧会通过限制激活诱导的细胞因子去氨酶 (AID) 表达来影响抗体类别转换为IgG2c.
- 由于B细胞中的pVHL缺乏,构成性HIF稳定减少了GCB细胞,高亲和性IgG的产生和B细胞的记忆.
- 低氧和HIF诱导抑制mTORC1活动,导致B细胞扩张,AID表达和抗体产生能力降低.
结论:
- 在GC中区域性缺氧是一种正常的生理特征,通过依赖HIF的氧气传感来调节B细胞功能.
- 氧气水平的调节失调或HIF信号破坏体内免疫力,影响抗体质量和记忆反应.
- 这些发现表明淋巴体器官的氧气可用性是调节幽默免疫力的关键因素,对病理生理学和疫苗设计有影响.
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