1. Distinct B cell subsets give rise to antigen-specific antibody responses against SARS-CoV-2
- Author
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Nai-Ying Zheng, Robert Jedrzejczak, Kumaran Shanmugarajah, Yoshihiro Kawaoka, Florian Krammer, Maud O. Jansen, Min Huang, Isabelle Stewart, Ya-Nan Dai, Jenna J. Guthmiller, Haley L. Dugan, Jun Huang, Lei Li, Nicholas Asby, Peter Halfmann, Andrzej Joachimiak, Olivia Stovicek, Maria Lucia Madariaga, Siriruk Changrob, Fatima Amanat, Jiaolong Wang, Paige D. Hall, Patrick C. Wilson, Henry A. Utset, Christopher A. Nelson, Daved H. Fremont, and Christopher T. Stamper
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medicine.drug_class ,Biology ,Monoclonal antibody ,Virology ,Article ,Epitope ,Affinity maturation ,Open reading frame ,medicine.anatomical_structure ,Antigen ,Immunity ,medicine ,Memory B cell ,B cell - Abstract
Discovery of durable memory B cell (MBC) subsets against neutralizing viral epitopes is critical for determining immune correlates of protection from SARS-CoV-2 infection. Here, we identified functionally distinct SARS-CoV-2-reactive B cell subsets by profiling the repertoire of convalescent COVID-19 patients using a high-throughput B cell sorting and sequencing platform. Utilizing barcoded SARS-CoV-2 antigen baits, we isolated thousands of B cells that segregated into discrete functional subsets specific for the spike, nucleocapsid protein (NP), and open reading frame (ORF) proteins 7a and 8. Spike-specific B cells were enriched in canonical MBC clusters, and monoclonal antibodies (mAbs) from these cells were potently neutralizing. By contrast, B cells specific to ORF8 and NP were enriched in naïve and innate-like clusters, and mAbs against these targets were exclusively non-neutralizing. Finally, we identified that B cell specificity, subset distribution, and affinity maturation were impacted by clinical features such as age, sex, and symptom duration. Together, our data provide a comprehensive tool for evaluating B cell immunity to SARS-CoV-2 infection or vaccination and highlight the complexity of the human B cell response to SARS-CoV-2.
- Published
- 2020
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