Longitudinal single-cell analysis of SARS-CoV-2-reactive B cells uncovers persistence of early-formed, antigen-specific clones
(2023) In JCI Insight 8(1). p.1-19- 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... (More)
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.
(Less)
- author
- Scharf, Lydia
; Axelsson, Hannes
; Emmanouilidi, Aikaterini
; Mathew, Nimitha R
; Sheward, Daniel J
; Leach, Susannah
; Isakson, Pauline
; Smirnov, Ilya V
; Marklund, Emelie
; Miron, Nicolae
; Andersson, Lars-Magnus
; Gisslén, Magnus
; Murrell, Ben
; Lundgren, Anna
; Bemark, Mats
LU
and Angeletti, Davide
(Less) - publishing date
- 2023-01-10
- type
- Contribution to journal
- publication status
- published
- keywords
- Humans, SARS-CoV-2, COVID-19, B-Lymphocytes, Plasma Cells, Clone Cells
- in
- JCI Insight
- volume
- 8
- issue
- 1
- pages
- 1 - 19
- publisher
- The American Society for Clinical Investigation
- external identifiers
-
- pmid:36445762
- scopus:85145966419
- ISSN
- 2379-3708
- DOI
- 10.1172/jci.insight.165299
- language
- English
- LU publication?
- no
- id
- e3688caa-ecac-45f3-9854-651e571f3338
- date added to LUP
- 2023-11-16 12:55:16
- date last changed
- 2025-01-20 21:20:58
@article{e3688caa-ecac-45f3-9854-651e571f3338,
abstract = {{<p>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.</p>}},
author = {{Scharf, Lydia and Axelsson, Hannes and Emmanouilidi, Aikaterini and Mathew, Nimitha R and Sheward, Daniel J and Leach, Susannah and Isakson, Pauline and Smirnov, Ilya V and Marklund, Emelie and Miron, Nicolae and Andersson, Lars-Magnus and Gisslén, Magnus and Murrell, Ben and Lundgren, Anna and Bemark, Mats and Angeletti, Davide}},
issn = {{2379-3708}},
keywords = {{Humans; SARS-CoV-2; COVID-19; B-Lymphocytes; Plasma Cells; Clone Cells}},
language = {{eng}},
month = {{01}},
number = {{1}},
pages = {{1--19}},
publisher = {{The American Society for Clinical Investigation}},
series = {{JCI Insight}},
title = {{Longitudinal single-cell analysis of SARS-CoV-2-reactive B cells uncovers persistence of early-formed, antigen-specific clones}},
url = {{http://dx.doi.org/10.1172/jci.insight.165299}},
doi = {{10.1172/jci.insight.165299}},
volume = {{8}},
year = {{2023}},
}