iScience (Mar 2023)

Demultiplexing Ig repertoires by parallel mRNA/DNA sequencing shows major differential alterations in severe COVID-19

  • Virginie Pascal,
  • Marine Dupont,
  • Paco de Rouault,
  • David Rizzo,
  • Delphine Rossille,
  • Robin Jeannet,
  • Thomas Daix,
  • Bruno François,
  • Steve Genebrier,
  • Marie Cornic,
  • Guillaume Monneret,
  • Fabienne Venet,
  • Juliette Ferrant,
  • Mikael Roussel,
  • Florian Reizine,
  • Mathieu Le Souhaitier,
  • Jean-Marc Tadié,
  • Karin Tarte,
  • Jean Feuillard,
  • Michel Cogné

Journal volume & issue
Vol. 26, no. 3
p. 106260

Abstract

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Summary: 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.

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