Profiling B cell immunodominance after SARS-CoV-2 infection reveals antibody evolution to non-neutralizing viral targets

被引：91

作者：

Dugan, Haley L. ^{[1
]}

Stamper, Christopher T. ^{[1
]}

Li, Lei ^{[2
]}

Changrob, Siriruk ^{[2
]}

Asby, Nicholas W. ^{[3
]}

Halfmann, Peter J. ^{[4
]}

Zheng, Nai-Ying ^{[2
]}

Huang, Min ^{[2
]}

Shaw, Dustin G. ^{[1
]}

Cobb, Mari S. ^{[5
]}

Erickson, Steven A. ^{[2
]}

Guthmiller, Jenna J. ^{[2
]}

Stovicek, Olivia ^{[2
]}

Wang, Jiaolong ^{[2
]}

Winkler, Emma S. ^{[6
,7
]}

Madariaga, Maria Lucia ^{[9
]}

Shanmugarajah, Kumaran ^{[9
]}

Jansen, Maud O. ^{[10
]}

Amanat, Fatima ^{[11
]}

Stewart, Isabelle ^{[2
,16
]}

Utset, Henry A. ^{[2
]}

Huang, Jun ^{[1
,3
]}

Nelson, Christopher A. ^{[6
]}

Dai, Ya-Nan ^{[6
]}

Hall, Paige D. ^{[6
]}

Jedrzejczak, Robert P. ^{[12
,13
]}

Joachimiak, Andrzej ^{[12
,13
,14
]}

Krammer, Florian ^{[11
]}

Diamond, Michael S. ^{[6
,7
,8
]}

Fremont, Daved H. ^{[6
]}

Kawaoka, Yoshihiro ^{[4
,15
]}

Wilson, Patrick C. ^{[1
,2
]}

机构：

[1] Univ Chicago, Comm Immunol, Chicago, IL 60637 USA

[2] Univ Chicago, Sect Rheumatol, Dept Med, Chicago, IL 60637 USA

[3] Univ Chicago, Pritzker Sch Mol Engn, Chicago, IL 60637 USA

[4] Univ Wisconsin, Dept Pathobiol Sci, Sch Vet Med, Influenza Res Inst, Madison, WI 53711 USA

[5] Univ Chicago, Sect Genet Med, Chicago, IL 60637 USA

[6] Washington Univ, Dept Med, Sch Med, St Louis, MO 63130 USA

[7] Washington Univ, Dept Pathol & Immunol, Sch Med, St Louis, MO 63130 USA

[8] Washington Univ, Dept Mol Immunol, Sch Med, St Louis, MO 63130 USA

[9] Univ Chicago, Dept Surg, Chicago, IL 60637 USA

[10] Univ Chicago, Dept Med, Chicago, IL 60637 USA

[11] Icahn Sch Med Mt Sinai, Dept Microbiol, New York, NY 10029 USA

[12] Univ Chicago, Ctr Struct Genom Infect Dis, Consortium Adv Sci & Engn, Chicago, IL 60439 USA

[13] Argonne Natl Lab, Struct Biol Ctr, Xray Sci Div, Lemont, IL 60439 USA

[14] Univ Chicago, Dept Biochem & Mol Biol, Chicago, IL 60637 USA

[15] Univ Tokyo, Inst Med Sci, Dept Microbiol & Immunol, Div Virol, Tokyo 1088639, Japan

[16] Victoria Univ Wellington, Sch Biol Sci, Wellington 6012, New Zealand

来源：

IMMUNITY | 2021年 / 54卷 / 06期

基金：

美国国家卫生研究院;

关键词：

GERMINAL CENTER; MARGINAL ZONE; MEMORY; ACTIVATION; EXPRESSION; IDENTIFICATION; PROLIFERATION; MATURATION; SIGNATURES; SURVIVAL;

D O I：

10.1016/j.immuni.2021.05.001

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Dissecting the evolution of memory B cells (MBCs) against SARS-CoV-2 is critical for understanding antibody recallupon secondary exposure. Here, we usedsingle-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 highlymutated 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.

引用

页码：1290 / +

页数：21

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