Profiling B cell immunodominance after SARS-CoV-2 infection reveals antibody evolution to non-neutralizing viral targets.
Profiling B cell immunodominance after SARS-CoV-2 infection reveals antibody evolution to non-neutralizing viral targets.
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DOI：
10.1016/j.immuni.2021.05.001
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发表时间：
2021-06-08
期刊：
影响因子：
32.4
通讯作者：
Wilson PC
中科院分区：
文献类型：
--
作者：
Dugan HL;Stamper CT;Li L;Changrob S;Asby NW;Halfmann PJ;Zheng NY;Huang M;Shaw DG;Cobb MS;Erickson SA;Guthmiller JJ;Stovicek O;Wang J;Winkler ES;Madariaga ML;Shanmugarajah K;Jansen MO;Amanat F;Stewart I;Utset HA;Huang J;Nelson CA;Dai YN;Hall PD;Jedrzejczak RP;Joachimiak A;Krammer F;Diamond MS;Fremont DH;Kawaoka Y;Wilson PC
解剖针对SARS-CoV-2的记忆B细胞(MBCs)的进化对于理解二次暴露时的抗体回忆至关重要。在这里，我们使用单细胞测序法对38名新冠肺炎患者的SARS-CoV-2反应性B细胞进行了分析。利用寡聚标记的抗原诱饵，我们分离了针对SARS-CoV-2尖峰蛋白、核蛋白(NP)、开放阅读框架8(ORF8)和地方性人类冠状病毒(HCoV)尖峰蛋白的B细胞。症状出现几个月后，SARS-CoV-2刺激性细胞在急性感染和恢复期患者的记忆室中丰富。在严重的急性感染中，大量的地方性HCoV反应性抗体分泌细胞被鉴定出来，并具有高度突变的可变基因，这意味着先前存在的免疫。最后，随着时间的推移，MBCs对NP和ORF8表现出明显的成熟，特别是在老年患者中。在体内，针对这些靶点的单抗是非中和的，也是非保护性的。这些发现揭示了感染过程中抗体对非中和细胞内抗原的适应性，强调了疫苗接种对诱导中和棘波特异的MBC的重要性。Dugan等人。使用多抗原诱饵分类和单细胞测序方法来分析SARS-CoV-2感染时B细胞的免疫优势，揭示随着时间的推移向内部病毒蛋白进化的动态反应。体内针对内部蛋白的抗体是非保护性的，这突显了疫苗接种对于产生尖峰主导的免疫记忆的重要性。
Dissecting the evolution of memory B cells (MBCs) against SARS-CoV-2 is critical for understanding antibody recall upon secondary exposure. Here, we used single-cell sequencing to profile SARS-CoV-2-reactive B cells in 38 COVID-19 patients. Using oligo-tagged antigen baits, we isolated B cells specific to the SARS-CoV-2 spike, nucleoprotein (NP), open reading frame 8 (ORF8), and endemic human coronavirus (HCoV) spike proteins. SARS-CoV-2 spike-specific cells were enriched in the memory compartment of acutely infected and convalescent patients several months post symptom onset. With severe acute infection, substantial populations of endemic HCoV-reactive antibody-secreting cells were identified and possessed highly mutated variable genes, signifying preexisting immunity. Finally, MBCs exhibited pronounced maturation to NP and ORF8 over time, especially in older patients. Monoclonal antibodies against these targets were non-neutralizing and non-protective in vivo. These findings reveal antibody adaptation to non-neutralizing intracellular antigens during infection, emphasizing the importance of vaccination for inducing neutralizing spike-specific MBCs. Dugan et al. use a multi-antigen bait sorting and single-cell sequencing approach to profile B cell immunodominance upon SARS-CoV-2 infection, revealing a dynamic response that evolves toward internal virus proteins over time. Antibodies to internal proteins were non-protective in vivo, highlighting the importance of vaccination for generating spike-dominated immune memory.
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影响因子：
64.8
作者：
Gaebler C;Wang Z;Lorenzi JCC;Muecksch F;Finkin S;Tokuyama M;Cho A;Jankovic M;Schaefer-Babajew D;Oliveira TY;Cipolla M;Viant C;Barnes CO;Bram Y;Breton G;Hägglöf T;Mendoza P;Hurley A;Turroja M;Gordon K;Millard KG;Ramos V;Schmidt F;Weisblum Y;Jha D;Tankelevich M;Martinez-Delgado G;Yee J;Patel R;Dizon J;Unson-O'Brien C;Shimeliovich I;Robbiani DF;Zhao Z;Gazumyan A;Schwartz RE;Hatziioannou T;Bjorkman PJ;Mehandru S;Bieniasz PD;Caskey M;Nussenzweig MC
通讯作者：
Nussenzweig MC
DOI：
10.1084/jem.20081571
发表时间：
2009-01-16
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Dienz O;Eaton SM;Bond JP;Neveu W;Moquin D;Noubade R;Briso EM;Charland C;Leonard WJ;Ciliberto G;Teuscher C;Haynes L;Rincon M
通讯作者：
Rincon M
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
影响因子：
6.4
作者：
Guthmiller JJ;Stovicek O;Wang J;Changrob S;Li L;Halfmann P;Zheng NY;Utset H;Stamper CT;Dugan HL;Miller WD;Huang M;Dai YN;Nelson CA;Hall PD;Jansen M;Shanmugarajah K;Donington JS;Krammer F;Fremont DH;Joachimiak A;Kawaoka Y;Tesic V;Madariaga ML;Wilson PC
通讯作者：
Wilson PC
影响因子：
4.4
作者：
Krzyzak, Lena;Seitz, Christine;Nitschke, Lars
通讯作者：
Nitschke, Lars