tetano
Editor, Senior Moderator
Cell Rep
. 2021 Jun 22;35(12):109286.
doi: 10.1016/j.celrep.2021.109286.
Single-cell BCR and transcriptome analysis after influenza infection reveals spatiotemporal dynamics of antigen-specific B cells
Nimitha R Mathew[SUP] 1 [/SUP], Jayalal K Jayanthan[SUP] 1 [/SUP], Ilya V Smirnov[SUP] 1 [/SUP], Jonathan L Robinson[SUP] 2 [/SUP], Hannes Axelsson[SUP] 1 [/SUP], Sravya S Nakka[SUP] 1 [/SUP], Aikaterini Emmanouilidi[SUP] 1 [/SUP], Paulo Czarnewski[SUP] 3 [/SUP], William T Yewdell[SUP] 4 [/SUP], Karin Schön[SUP] 1 [/SUP], Cristina Lebrero-Fernández[SUP] 1 [/SUP], Valentina Bernasconi[SUP] 1 [/SUP], William Rodin[SUP] 1 [/SUP], Ali M Harandi[SUP] 5 [/SUP], Nils Lycke[SUP] 1 [/SUP], Nicholas Borcherding[SUP] 6 [/SUP], Jonathan W Yewdell[SUP] 7 [/SUP], Victor Greiff[SUP] 8 [/SUP], Mats Bemark[SUP] 9 [/SUP], Davide Angeletti[SUP] 10 [/SUP]
Affiliations
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 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.
Keywords: B cells; antibodies; antiviral immunity; germinal center; influenza; memory B cells; single-cell BCRseq; single-cell RNA-seq.
. 2021 Jun 22;35(12):109286.
doi: 10.1016/j.celrep.2021.109286.
Single-cell BCR and transcriptome analysis after influenza infection reveals spatiotemporal dynamics of antigen-specific B cells
Nimitha R Mathew[SUP] 1 [/SUP], Jayalal K Jayanthan[SUP] 1 [/SUP], Ilya V Smirnov[SUP] 1 [/SUP], Jonathan L Robinson[SUP] 2 [/SUP], Hannes Axelsson[SUP] 1 [/SUP], Sravya S Nakka[SUP] 1 [/SUP], Aikaterini Emmanouilidi[SUP] 1 [/SUP], Paulo Czarnewski[SUP] 3 [/SUP], William T Yewdell[SUP] 4 [/SUP], Karin Schön[SUP] 1 [/SUP], Cristina Lebrero-Fernández[SUP] 1 [/SUP], Valentina Bernasconi[SUP] 1 [/SUP], William Rodin[SUP] 1 [/SUP], Ali M Harandi[SUP] 5 [/SUP], Nils Lycke[SUP] 1 [/SUP], Nicholas Borcherding[SUP] 6 [/SUP], Jonathan W Yewdell[SUP] 7 [/SUP], Victor Greiff[SUP] 8 [/SUP], Mats Bemark[SUP] 9 [/SUP], Davide Angeletti[SUP] 10 [/SUP]
Affiliations
- PMID: 34161770
- DOI: 10.1016/j.celrep.2021.109286
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 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.
Keywords: B cells; antibodies; antiviral immunity; germinal center; influenza; memory B cells; single-cell BCRseq; single-cell RNA-seq.