Single-cell BCR and transcriptome analysis after influenza infection reveals spatiotemporal dynamics of antigen-specific B cells

Nimitha R. Mathew, Jayalal K. Jayanthan, Ilya V. Smirnov, Jonathan L. Robinson, Hannes Axelsson, Sravya S. Nakka, Aikaterini Emmanouilidi, Paulo Czarnewski, William T. Yewdell, Karin Schön, Cristina Lebrero-Fernández, Valentina Bernasconi, William Rodin, Ali M. Harandi, Nils Lycke, Nicholas Borcherding, Jonathan W. Yewdell, Victor Greiff, Mats Bemark, Davide Angeletti

Research output: Contribution to journalArticlepeer-review

62 Scopus citations

Abstract

B cell responses are critical for antiviral immunity. However, a comprehensive picture of antigen-specific B cell differentiation, clonal proliferation, and dynamics in different organs after infection is lacking. Here, by combining single-cell RNA and B cell receptor (BCR) sequencing of antigen-specific cells in lymph nodes, spleen, and lungs after influenza infection in mice, we identify several germinal center (GC) B cell subpopulations and organ-specific differences that persist over the course of the response. We discover transcriptional differences between memory cells in lungs and lymphoid organs and organ-restricted clonal expansion. Remarkably, we find significant clonal overlap between GC-derived memory and plasma cells. By combining BCR-mutational analyses with monoclonal antibody (mAb) expression and affinity measurements, we find that memory B cells are highly diverse and can be selected from both low- and high-affinity precursors. By linking antigen recognition with transcriptional programming, clonal proliferation, and differentiation, these finding provide important advances in our understanding of antiviral immunity.

Original languageEnglish
Article number109286
JournalCell Reports
Volume35
Issue number12
DOIs
StatePublished - Jun 22 2021

Keywords

  • B cells
  • antibodies
  • antiviral immunity
  • germinal center
  • influenza
  • memory B cells
  • single-cell BCRseq
  • single-cell RNA-seq

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