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Status |
Public on May 29, 2021 |
Title |
The healing myocardium mobilizes a distinct B-cell subset through a CXCL13-CXCR5-dependent mechanism |
Organism |
Mus musculus |
Experiment type |
Expression profiling by high throughput sequencing Other
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Summary |
Recent studies have revealed that B-cells can influence post-myocardial infarction (MI) inflammation and repair, but the mechanisms controlling their mobilization and in situ activity remain poorly understood. Herein, we sought to dissect the mechanisms underlying B-cell cardiotropism and assess the B-cell antigen specificity profile in an experimental model of MI. Our study reveals that B-cells that are not antigen-specifically expanded readily infiltrate the infarcted myocardium via the CXCL13-CXCR5 axis. The restricted distribution of CXCR5 among hB cells could offer a suitable opportunity to selectively target this leukocyte subset therapeutically while minimally interfering with other local or systemic immunological processes.
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Overall design |
Histological, flow cytometry and single-cell RNA-sequencing (scRNAseq) analyses revealed the rapid accumulation of diverse B-cell subsets in the murine infarcted myocardium, including a distinct B-cell cluster exclusively found in the heart (hB). The hB-cells exhibited upregulated expression of activation markers (e.g., Cd69) and expressed high levels of C-C-chemokine receptor type 7 (CCR7) and CXC-chemokine receptor type 5 (CXCR5). This distinct chemokine receptor signature was not shared with any other cell population in the healing myocardium. Moreover, we detected a myocardial gradient of CXC-motif chemokine ligand 13 (CXCL13, the ligand of CXCR5) in the early post-MI inflammatory (d1) and healing (d5) phases. Notably, mice treated with a neutralizing CXCL13-specific antibody showed reduced infiltration of myocardial B-cells after MI compared to control animals. Finally, global B-cell receptor (BCR) repertoire analyses revealed that the vast majority of B-cells infiltrating the infarcted myocardium were not clonally expanded and showed no sign of antigen specificity. In addition to the in situ B-cell responses, slight clonal expansion of a few germinal centre B-cells (GCs) was detected in the mediastinal lymph nodes (med-LNs).
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Contributor(s) |
Heinrichs M, Ashour D, Büchner L, Wedekind G, Heinze K, Arampatzi P, Saliba A, Cochain C, Hofmann U, Frantz S, Ramos G |
Citation(s) |
34048536 |
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Submission date |
May 08, 2020 |
Last update date |
May 31, 2021 |
Contact name |
Antoine-Emmanuel Saliba |
E-mail(s) |
emmanuel.saliba@helmholtz-hzi.de
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Phone |
+49-931-31-81341
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Organization name |
Helmholtz Institute for RNA-based Infection Research
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Street address |
Josef-Schneider-Straße 2 / D15
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City |
Würzburg |
ZIP/Postal code |
97080 |
Country |
Germany |
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Platforms (1) |
GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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Samples (1) |
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Relations |
BioProject |
PRJNA631246 |
SRA |
SRP260808 |
Supplementary file |
Size |
Download |
File type/resource |
GSE150140_RAW.tar |
468.6 Mb |
(http)(custom) |
TAR (of CSV, H5, TAR) |
SRA Run Selector |
Raw data are available in SRA |
Processed data provided as supplementary file |
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