在SARS-CoV-2感染期间,未切换的记忆B细胞通过激活和促炎性细胞因子的产生
Moriah J Castleman1, Adriana Luna Santos1, Kelsey E Lesteberg1,2
1Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, CO, United States.
严重的SARS-CoV2感染会减少未切换的记忆B细胞,增加诸如TNFα之类的促炎细胞因子. 这些B细胞表现出增强的激活和增强的信号传递,有助于病毒感染期间的炎症反应.
科学领域:
- 免疫学 免疫学 免疫学
- 病毒学 病毒学
- 细胞生物学 细胞生物学
背景情况:
- 记忆B细胞对于适应性免疫至关重要,包括未切换 (CD27+IgD+) 和切换 (CD27+IgD-) 的子集.
- 与切换记忆B细胞相比,未切换记忆B细胞在人类免疫中的作用不太清楚.
- 据报道,在严重的SARS-CoV-2感染中,未切换的记忆B细胞减少.
研究的目的:
- 调查SARS-CoV-2感染中未切换的记忆B细胞的激活状态,B细胞受体 (BCR) 功能和细胞因子产生.
- 将这些特征与健康人群,SARS-CoV-2-接种疫苗的人群和患有轻度或重度COVID-19的人群进行比较.
- 阐明B细胞在病毒感染期间对炎症反应的贡献.
主要方法:
- 分析来自不同人群的全血样本,使用流细胞计和免疫学检测.
- 描述B细胞子集,包括未切换和切换的B细胞.
- 评估BCR信号传递,受体表达 (例如CD72),和细胞因子产生 (例如IL-6,TNFα) 作为对病毒刺激的反应.
主要成果:
- 严重的SARS-CoV-2感染与未切换记忆B细胞的频率降低和全身TNFα的增加有关.
- 只有"IgD+"内存B细胞的频率增加与严重感染中较高的IgG自身抗体水平相关.
- 来自严重COVID-19患者的未切换和切换的B细胞都表现出高度激活,减少CD72表达和增强BCR信号.
- 轻度SARS-CoV-2感染的B细胞在病毒TLR连接体刺激时产生促炎细胞因子IL-6 (未切换) 和TNFα (切换).
结论:
- 严重的SARS-CoV-2感染显著影响记忆B细胞种群,特别是减少未切换的子集.
- 在严重的COVID-19期间,B细胞,特别是未切换和切换的记忆群体,表现出高度激活和增强的信号传导能力.
- 在病毒感染期间,B细胞通过产生IL-6和TNFα等关键细胞因子,积极促进炎症环境.
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