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Article ; Online: Longitudinal single-cell analysis of SARS-CoV-2–reactive B cells uncovers persistence of early-formed, antigen-specific clones

Lydia Scharf / Hannes Axelsson / Aikaterini Emmanouilidi / Nimitha R. Mathew / Daniel J. Sheward / Susannah Leach / Pauline Isakson / Ilya V. Smirnov / Emelie Marklund / Nicolae Miron / Lars-Magnus Andersson / Magnus Gisslén / Ben Murrell / Anna Lundgren / Mats Bemark / Davide Angeletti

JCI Insight, Vol 8, Iss

2023  Volume 1

Abstract: Understanding persistence and evolution of B cell clones after COVID-19 infection and vaccination is crucial for predicting responses against emerging viral variants and optimizing vaccines. Here, we collected longitudinal samples from patients with ... ...

Abstract Understanding persistence and evolution of B cell clones after COVID-19 infection and vaccination is crucial for predicting responses against emerging viral variants and optimizing vaccines. Here, we collected longitudinal samples from patients with severe COVID-19 every third to seventh day during hospitalization and every third month after recovery. We profiled their antigen-specific immune cell dynamics by combining single-cell RNA-Seq, Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITE-Seq), and B cell receptor–Seq (BCR-Seq) with oligo-tagged antigen baits. While the proportion of Spike receptor binding domain–specific memory B cells (MBC) increased from 3 months after infection, the other Spike- and Nucleocapsid-specific B cells remained constant. All patients showed ongoing class switching and sustained affinity maturation of antigen-specific cells, and affinity maturation was not significantly increased early after vaccine. B cell analysis revealed a polyclonal response with limited clonal expansion; nevertheless, some clones detected during hospitalization, as plasmablasts, persisted for up to 1 year, as MBC. Monoclonal antibodies derived from persistent B cell families increased their binding and neutralization breadth and started recognizing viral variants by 3 months after infection. Overall, our findings provide important insights into the clonal evolution and dynamics of antigen-specific B cell responses in longitudinally sampled patients infected with COVID-19.
Keywords COVID-19 ; Immunology ; Medicine ; R
Subject code 570
Language English
Publishing date 2023-01-01T00:00:00Z
Publisher American Society for Clinical investigation
Document type Article ; Online
Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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