Demultiplexing Ig repertoires by parallel mRNA/DNA sequencing shows major differential alterations in severe COVID-19.
Immunology
Respiratory medicine
Journal
iScience
ISSN: 2589-0042
Titre abrégé: iScience
Pays: United States
ID NLM: 101724038
Informations de publication
Date de publication:
17 Mar 2023
17 Mar 2023
Historique:
received:
31
08
2022
revised:
14
01
2023
accepted:
17
02
2023
pubmed:
28
2
2023
medline:
28
2
2023
entrez:
27
2
2023
Statut:
ppublish
Résumé
To understand the fine differential elements that can lead to or prevent acute respiratory distress syndrome (ARDS) in COVID-19 patients, it is crucial to investigate the immune response architecture. We herein dissected the multiple layers of B cell responses by flow cytometry and Ig repertoire analysis from acute phase to recovery. Flow cytometry with FlowSOM analysis showed major changes associated with COVID-19 inflammation such as an increase of double-negative B-cells and ongoing plasma cell differentiation. This paralleled COVID-19-driven expansion of two disconnected B-cell repertoires. Demultiplexing successive DNA and RNA Ig repertoire patterns characterized an early expansion of IgG1 clonotypes with atypically long and uncharged CDR3, the abundance of this inflammatory repertoire being correlated with ARDS and likely pejorative. A superimposed convergent response included convergent anti-SARS-CoV-2 clonotypes. It featured progressively increasing somatic hypermutation together with normal-length or short CDR3 and it persisted until a quiescent memory B-cell stage after recovery.
Identifiants
pubmed: 36845033
doi: 10.1016/j.isci.2023.106260
pii: S2589-0042(23)00337-1
pmc: PMC9942447
doi:
Types de publication
Journal Article
Langues
eng
Pagination
106260Informations de copyright
© 2023 The Authors.
Déclaration de conflit d'intérêts
The authors declare no competing interest.
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