Single-cell BCR and transcriptome analysis after influenza infection reveals spatiotemporal dynamics of antigen-specific B cells
Journal article, 2021
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.
influenza
memory B cells
single-cell RNA-seq
B cells
antiviral immunity
germinal center
antibodies
single-cell BCRseq
Author
Nimitha R. Mathew
University of Gothenburg
Jayalal K. Jayanthan
University of Gothenburg
Ilya V. Smirnov
University of Gothenburg
Jonathan Robinson
Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology
Hannes Axelsson
University of Gothenburg
Sravya S. Nakka
University of Gothenburg
Aikaterini Emmanouilidi
University of Gothenburg
Paulo Czarnewski
Stockholm University
William T. Yewdell
Memorial Sloan-Kettering Cancer Center
Karin Schön
University of Gothenburg
Cristina Lebrero-Fernández
University of Gothenburg
V. Bernasconi
University of Gothenburg
William Rodin
University of Gothenburg
A. M. Harandi
University of Gothenburg
BC Children's Hospital Research Institute
N. Y. Lycke
University of Gothenburg
Nicholas Borcherding
Washington University in St. Louis
Jonathan W. Yewdell
National Institutes of Health, Bethesda
Victor Greiff
University of Oslo
Mats Bemark
Sahlgrenska University Hospital
University of Gothenburg
Davide Angeletti
University of Gothenburg
Cell Reports
22111247 (eISSN)
Vol. 35 12 109286Subject Categories
Cell and Molecular Biology
Immunology in the medical area
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
DOI
10.1016/j.celrep.2021.109286
PubMed
34161770