Single-cell BCR and transcriptome analysis after influenza infection reveals spatiotemporal dynamics of antigen-specific B cells
(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.
(Less)
- author
- publishing date
- 2021-06-22
- 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}}, }