Single-cell BCR and transcriptome analysis after influenza infection reveals spatiotemporal dynamics of antigen-specific B cells
Artikel i vetenskaplig tidskrift, 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.
antibodies
B cells
memory B cells
single-cell RNA-seq
influenza
germinal center
antiviral immunity
single-cell BCRseq
Författare
Nimitha R. Mathew
Göteborgs universitet
Jayalal K. Jayanthan
Göteborgs universitet
Ilya V. Smirnov
Göteborgs universitet
Jonathan Robinson
Chalmers, Biologi och bioteknik, Infrastrukturer
Hannes Axelsson
Göteborgs universitet
Sravya S. Nakka
Göteborgs universitet
Aikaterini Emmanouilidi
Göteborgs universitet
Paulo Czarnewski
Stockholms universitet
William T. Yewdell
Memorial Sloan-Kettering Cancer Center
Karin Schön
Göteborgs universitet
Cristina Lebrero-Fernández
Göteborgs universitet
V. Bernasconi
Göteborgs universitet
William Rodin
Göteborgs universitet
A. M. Harandi
Göteborgs universitet
University of British Columbia (UBC)
N. Y. Lycke
Göteborgs universitet
Nicholas Borcherding
Washington University in St. Louis
Jonathan W. Yewdell
National Institutes of Health (NIH)
Victor Greiff
Universitetet i Oslo
Mats Bemark
Sahlgrenska universitetssjukhuset
Göteborgs universitet
Davide Angeletti
Göteborgs universitet
Cell Reports
22111247 (eISSN)
Vol. 35 12 109286Ämneskategorier (SSIF 2011)
Cell- och molekylärbiologi
Immunologi inom det medicinska området
Medicinsk bioteknologi (med inriktning mot cellbiologi (inklusive stamcellsbiologi), molekylärbiologi, mikrobiologi, biokemi eller biofarmaci)
DOI
10.1016/j.celrep.2021.109286
PubMed
34161770