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

Cell Rep. 2021 Jun 22;35(12):109286. doi: 10.1016/j.celrep.2021.109286.

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.

Keywords: B cells; antibodies; antiviral immunity; germinal center; influenza; memory B cells; single-cell BCRseq; single-cell RNA-seq.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / metabolism
  • Antigens, Viral / immunology*
  • B-Lymphocytes / immunology*
  • Cell Differentiation / genetics
  • Cell Proliferation
  • Clone Cells
  • Gene Expression Profiling*
  • Germinal Center / immunology
  • Hemagglutinin Glycoproteins, Influenza Virus / immunology
  • Humans
  • Influenza, Human / genetics*
  • Influenza, Human / immunology*
  • Memory B Cells / metabolism
  • Mice, Inbred C57BL
  • Mutation / genetics
  • Mutation Rate
  • Organ Specificity
  • Plasma Cells / metabolism
  • RNA / metabolism
  • Receptors, Antigen, B-Cell / metabolism*
  • Single-Cell Analysis*
  • Transcription, Genetic

Substances

  • Antibodies, Monoclonal
  • Antigens, Viral
  • Hemagglutinin Glycoproteins, Influenza Virus
  • Receptors, Antigen, B-Cell
  • RNA