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.

influenza

memory B cells

single-cell RNA-seq

B cells

antiviral immunity

germinal center

antibodies

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, Systembiologi, CSBI

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

BC Children's Hospital Research Institute

N. Y. Lycke

Göteborgs universitet

Nicholas Borcherding

Washington University in St. Louis

Jonathan W. Yewdell

National Institutes of Health, Bethesda

Victor Greiff

Universitetet i Oslo

Mats Bemark

Sahlgrenska universitetssjukhuset

Göteborgs universitet

Davide Angeletti

Göteborgs universitet

Cell Reports

2211-1247 (ISSN)

Vol. 35 12 109286

Ämneskategorier

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

Mer information

Senast uppdaterat

2021-06-29