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

Mathew, Nimitha R ; Jayanthan, Jayalal K ; Smirnov, Ilya V ; Robinson, Jonathan L ; Axelsson, Hannes ; Nakka, Sravya S ; Emmanouilidi, Aikaterini ; Czarnewski, Paulo ; Yewdell, William T and Schön, Karin , et al. (2021) In Cell Reports 35(12). p.1-17
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... (More)

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.

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publishing date
type
Contribution to journal
publication status
published
keywords
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, 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
in
Cell Reports
volume
35
issue
12
article number
109286
pages
1 - 17
publisher
Cell Press
external identifiers
  • scopus:85108282008
  • pmid:34161770
ISSN
2211-1247
DOI
10.1016/j.celrep.2021.109286
language
English
LU publication?
no
additional info
Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.
id
a78f9861-a24f-40d9-9cf2-bd094a3c2478
date added to LUP
2023-11-16 14:58:10
date last changed
2024-04-14 17:02:44
@article{a78f9861-a24f-40d9-9cf2-bd094a3c2478,
  abstract     = {{<p>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.</p>}},
  author       = {{Mathew, Nimitha R and Jayanthan, Jayalal K and Smirnov, Ilya V and Robinson, Jonathan L and Axelsson, Hannes and Nakka, Sravya S and Emmanouilidi, Aikaterini and Czarnewski, Paulo and Yewdell, William T and Schön, Karin and Lebrero-Fernández, Cristina and Bernasconi, Valentina and Rodin, William and Harandi, Ali M and Lycke, Nils and Borcherding, Nicholas and Yewdell, Jonathan W and Greiff, Victor and Bemark, Mats and Angeletti, Davide}},
  issn         = {{2211-1247}},
  keywords     = {{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; 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}},
  language     = {{eng}},
  month        = {{06}},
  number       = {{12}},
  pages        = {{1--17}},
  publisher    = {{Cell Press}},
  series       = {{Cell Reports}},
  title        = {{Single-cell BCR and transcriptome analysis after influenza infection reveals spatiotemporal dynamics of antigen-specific B cells}},
  url          = {{http://dx.doi.org/10.1016/j.celrep.2021.109286}},
  doi          = {{10.1016/j.celrep.2021.109286}},
  volume       = {{35}},
  year         = {{2021}},
}