CD4+ follicular regulatory T cells optimize the influenza virus-specific B cell response.
CD4+ follicular regulatory T cells optimize the influenza virus-specific B cell response.
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CD4+滤泡调节性T细胞优化流感病毒特异性B细胞反应。
DOI：
10.1084/jem.20200547
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发表时间：
2021-03-01
期刊：
影响因子：
--
通讯作者：
Craft J
中科院分区：
文献类型：
--
作者：
Lu Y;Jiang R;Freyn AW;Wang J;Strohmeier S;Lederer K;Locci M;Zhao H;Angeletti D;O'Connor KC;Kleinstein SH;Nachbagauer R;Craft J
季节性流感病毒感染每年在全世界引起严重疾病和大量死亡。本研究表明，CD 4+滤泡调节性T细胞是流感病毒攻击后最佳抗原特异性体液免疫所必需的。CD 4+滤泡调节性T（Tfr）细胞通过调节滤泡辅助性T（Tfh）细胞和生发中心发育控制B细胞反应，同时抑制自身反应性;然而，它们在生产性生发中心B细胞反应和体液记忆调节中的作用尚未完全确定。我们发现，Tfr细胞促进流感病毒感染后抗原特异性生发中心B细胞反应。在病毒攻击后，我们发现Tfr细胞对于病毒特异性、长寿浆细胞的稳健产生、针对两种主要流感病毒糖蛋白血凝素（HA）和神经氨酸酶（NA）的抗体产生以及BCR库的适当调节是必需的。为了进一步研究Tfr细胞在病毒攻击过程中的功能相关性，我们使用了一种连续免疫模型，反复暴露于抗原性部分保守的流感病毒株，揭示了Tfr细胞促进针对保守的HA茎区的回忆抗体应答。因此，Tfr细胞促进抗原特异性B细胞应答，并且对于长期体液记忆的发展是必需的。
Seasonal influenza virus infections cause severe illness and a substantial number of deaths worldwide every year. This study reveals that the CD4+ follicular regulatory T cells are necessary for optimal antigen-specific humoral immunity following influenza virus challenge. CD4+ follicular regulatory T (Tfr) cells control B cell responses through the modulation of follicular helper T (Tfh) cells and germinal center development while suppressing autoreactivity; however, their role in the regulation of productive germinal center B cell responses and humoral memory is incompletely defined. We show that Tfr cells promote antigen-specific germinal center B cell responses upon influenza virus infection. Following viral challenge, we found that Tfr cells are necessary for robust generation of virus-specific, long-lived plasma cells, antibody production against both hemagglutinin (HA) and neuraminidase (NA), the two major influenza virus glycoproteins, and appropriate regulation of the BCR repertoire. To further investigate the functional relevance of Tfr cells during viral challenge, we used a sequential immunization model with repeated exposure of antigenically partially conserved strains of influenza viruses, revealing that Tfr cells promote recall antibody responses against the conserved HA stalk region. Thus, Tfr cells promote antigen-specific B cell responses and are essential for the development of long-term humoral memory.
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影响因子：
30.5
作者：
Clement, Rachel L.;Daccache, Joe;Sage, Peter T.
通讯作者：
Sage, Peter T.
影响因子：
32.4
作者：
Marshall HD;Chandele A;Jung YW;Meng H;Poholek AC;Parish IA;Rutishauser R;Cui W;Kleinstein SH;Craft J;Kaech SM
通讯作者：
Kaech SM
影响因子：
32.4
作者：
Joshi NS;Akama-Garren EH;Lu Y;Lee DY;Chang GP;Li A;DuPage M;Tammela T;Kerper NR;Farago AF;Robbins R;Crowley DM;Bronson RT;Jacks T
通讯作者：
Jacks T
影响因子：
24.8
作者：
Laidlaw BJ;Lu Y;Amezquita RA;Weinstein JS;Vander Heiden JA;Gupta NT;Kleinstein SH;Kaech SM;Craft J
通讯作者：
Craft J
影响因子：
17.1
作者：
Andrews SF;Huang Y;Kaur K;Popova LI;Ho IY;Pauli NT;Henry Dunand CJ;Taylor WM;Lim S;Huang M;Qu X;Lee JH;Salgado-Ferrer M;Krammer F;Palese P;Wrammert J;Ahmed R;Wilson PC
通讯作者：
Wilson PC