Tfh cells and the germinal center are required for memory B cell formation & humoral immunity after ChAdOx1 nCoV-19 vaccination.

Tfh cells and the germinal center are required for memory B cell formation & humoral immunity after ChAdOx1 nCoV-19 vaccination.
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DOI:
10.1016/j.xcrm.2022.100845
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发表时间:
2022-12-20
影响因子:
14.3
通讯作者:
Linterman, Michelle A.
Linterman, Michelle A.
中科院分区:
医学1区
文献类型:
--
作者:
Foster, William S.;Lee, Jia Le;Thakur, Nazia;Newman, Joseph;Spencer, Alexandra J.;Davies, Sophie;Woods, Danielle;Godfrey, Leila;Hay, Iain M.;Innocentin, Silvia;Yam-Puc, Juan Carlos;Horner, Emily C.;Sharpe, Hayley J.;Thaventhiran, James E.;Bailey, Dalan;Lambe, Teresa;Linterman, Michelle A.

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有效疫苗的推出促进了严重急性呼吸道综合征冠状病毒2型(SARS-CoV-2)大流行的出现。成功的疫苗产生高亲和力的血浆母细胞和长寿命的保护性记忆B细胞。在这里,我们展示了ChAdOx 1 nCoV-19疫苗接种后最佳血清抗体和记忆B细胞形成对T滤泡辅助(Tfh)细胞和生发中心反应的要求。我们发现Tfh细胞在扩增抗原特异性B细胞同时鉴定Tfh细胞依赖性和非依赖性记忆B细胞亚群中起重要作用。在二次接种后,在初次免疫期间产生的生殖中心B细胞可以再次被召回作为生殖中心B细胞。同样地,初次免疫GC-Tfh细胞可以作为Tfh或Th 1细胞回忆,突出了Tfh细胞记忆的多能性。这项研究表明,ChAdOx 1 nCoV-19诱导的生发中心是体液免疫的关键来源。Tfh细胞是ChAdOx 1 nCoV-19疫苗接种后RBD+ B细胞选择所必需的GC B细胞的缺乏限制了RBD+ B细胞扩增和血清免疫性RBD+ B细胞在二次应答期间被召回GC Tfh细胞在二次应答期间被召回作为Tfh细胞或作为Th 1细胞有效的疫苗引发保护性体液免疫。Foster等人使用高参数流式细胞术和共聚焦显微镜来证明疫苗诱导的生发中心是ChAdOx 1 nCoV-19疫苗接种后体液免疫的关键来源。
Emergence from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has been facilitated by the rollout of effective vaccines. Successful vaccines generate high-affinity plasma blasts and long-lived protective memory B cells. Here, we show a requirement for T follicular helper (Tfh) cells and the germinal center reaction for optimal serum antibody and memory B cell formation after ChAdOx1 nCoV-19 vaccination. We found that Tfh cells play an important role in expanding antigen-specific B cells while identifying Tfh-cell-dependent and -independent memory B cell subsets. Upon secondary vaccination, germinal center B cells generated during primary immunizations can be recalled as germinal center B cells again. Likewise, primary immunization GC-Tfh cells can be recalled as either Tfh or Th1 cells, highlighting the pluripotent nature of Tfh cell memory. This study demonstrates that ChAdOx1 nCoV-19-induced germinal centers are a critical source of humoral immunity. Tfh cells are required for RBD+ B cell selection after ChAdOx1 nCoV-19 vaccination Absence of GC B cells limits RBD+ B cell expansion and serum immunity RBD+ B cells are recalled to the GC during secondary responses GC Tfh cells are recalled during secondary responses as Tfh cells or as Th1 cells Effective vaccines elicit protective humoral immunity. Foster et al. use high-parameter flow cytometry and confocal microscopy to demonstrate that vaccine-induced germinal centers are a critical source of humoral immunity following ChAdOx1 nCoV-19 vaccination.
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