High-affinity, neutralizing antibodies to SARS-CoV-2 can be made without T follicular helper cells.
High-affinity, neutralizing antibodies to SARS-CoV-2 can be made without T follicular helper cells.
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DOI：
10.1126/sciimmunol.abl5652
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发表时间：
2022-02-04
影响因子：
24.8
通讯作者：
Eisenbarth SC
中科院分区：
文献类型：
--
作者：
Chen JS;Chow RD;Song E;Mao T;Israelow B;Kamath K;Bozekowski J;Haynes WA;Filler RB;Menasche BL;Wei J;Alfajaro MM;Song W;Peng L;Carter L;Weinstein JS;Gowthaman U;Chen S;Craft J;Shon JC;Iwasaki A;Wilen CB;Eisenbarth SC
T滤泡辅助细胞(TFH)是以生发中心(GC)为基础的保护性抗病毒抗体反应的常规驱动细胞。然而，在严重的新冠肺炎患者中已经观察到TFH细胞和GC的丢失。由于在这些患者中T细胞-B细胞相互作用和免疫球蛋白类别转换仍然存在，因此在SARS-CoV-2感染期间可能存在非规范的抗体产生途径。我们发现，对于SARS-CoV-2感染、SARS-CoV-2疫苗接种和甲型流感病毒感染，都能诱导出Tfh依赖和非依赖的抗体。尽管抗SARS-CoV-2的TFH非依赖性抗体有证据表明减少了体细胞的超突变，但它们仍然是高亲和力的、持久的、对不同的尖峰衍生表位具有反应的，并且能够中和同源的SARS-CoV-2和所关注的B.1.351(Beta)变体。事实上，我们通过表位映射和BCR测序发现，TFH细胞专注于B细胞的反应，因此，在没有TFH细胞的情况下，保持了更多样化的克隆谱系。这些数据支持在病毒感染期间诱导B细胞反应的另一种途径，该途径能够产生有效的中和抗体来补充传统的GC衍生抗体，这些抗体可能补偿病毒炎症损伤的GC。互补的TFH细胞依赖和独立的抗体产生途径介导了对SARS-CoV-2的中和反应。
T follicular helper (Tfh) cells are the conventional drivers of protective, germinal center (GC)-based antiviral antibody responses. However, loss of Tfh cells and GCs has been observed in patients with severe COVID-19. As T cell-B cell interactions and immunoglobulin class switching still occur in these patients, non-canonical pathways of antibody production may be operative during SARS-CoV-2 infection. We found that both Tfh-dependent and -independent antibodies were induced against SARS-CoV-2 infection, SARS-CoV-2 vaccination, and influenza A virus infection. Even though Tfh-independent antibodies to SARS-CoV-2 had evidence of reduced somatic hypermutation, they were still high-affinity, durable, and reactive against diverse spike-derived epitopes and were capable of neutralizing both homologous SARS-CoV-2 and the B.1.351 (beta) variant of concern. Indeed, we found by epitope mapping and BCR sequencing that Tfh cells focused the B cell response and therefore, in the absence of Tfh cells, a more diverse clonal repertoire was maintained. These data support an alternative pathway for the induction of B cell responses during viral infection that enables effective, neutralizing antibody production to complement traditional GC-derived antibodies that might compensate for GCs damaged by viral inflammation. Complementary Tfh cell-dependent and -independent pathways of antibody production mediate neutralizing responses to SARS-CoV-2.
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DOI：
10.1084/jem.20101773
发表时间：
2011-05-09
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Fahey LM;Wilson EB;Elsaesser H;Fistonich CD;McGavern DB;Brooks DG
通讯作者：
Brooks DG
影响因子：
64.5
作者：
Dejnirattisai W;Zhou D;Ginn HM;Duyvesteyn HME;Supasa P;Case JB;Zhao Y;Walter TS;Mentzer AJ;Liu C;Wang B;Paesen GC;Slon-Campos J;López-Camacho C;Kafai NM;Bailey AL;Chen RE;Ying B;Thompson C;Bolton J;Fyfe A;Gupta S;Tan TK;Gilbert-Jaramillo J;James W;Knight M;Carroll MW;Skelly D;Dold C;Peng Y;Levin R;Dong T;Pollard AJ;Knight JC;Klenerman P;Temperton N;Hall DR;Williams MA;Paterson NG;Bertram FKR;Siebert CA;Clare DK;Howe A;Radecke J;Song Y;Townsend AR;Huang KA;Fry EE;Mongkolsapaya J;Diamond MS;Ren J;Stuart DI;Screaton GR
通讯作者：
Screaton GR
影响因子：
64.5
作者：
Hoffmann M;Arora P;Groß R;Seidel A;Hörnich BF;Hahn AS;Krüger N;Graichen L;Hofmann-Winkler H;Kempf A;Winkler MS;Schulz S;Jäck HM;Jahrsdörfer B;Schrezenmeier H;Müller M;Kleger A;Münch J;Pöhlmann S
通讯作者：
Pöhlmann S
影响因子：
4.4
作者：
Junt, T;Fink, K;Hengartner, H
通讯作者：
Hengartner, H
影响因子：
64.8
作者：
Crotty, S;Kersh, EN;Ahmed, R
通讯作者：
Ahmed, R