Autor: |
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 |
Rok vydání: |
2022 |
Zdroj: |
JCI insight. |
ISSN: |
2379-3708 |
Popis: |
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 severe COVID-19 patients every third to seventh day during hospitalization and every third month after recovery. We profiled the antigen-specific immune cell dynamics by combining single cell RNA-Seq, Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITE)-Seq, B cell receptor (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, which 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 one 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 COVID-19 infected patients. |
Databáze: |
OpenAIRE |
Externí odkaz: |
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