GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
Series GSE150140 Query DataSets for GSE150140
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
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.
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).
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
Submission date May 08, 2020
Last update date May 31, 2021
Contact name Antoine-Emmanuel Saliba
Phone +49-931-31-81341
Organization name Helmholtz Institute for RNA-based Infection Research
Street address Josef-Schneider-Straße 2 / D15
City Würzburg
ZIP/Postal code 97080
Country Germany
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (1)
GSM4524179 B lymphocytes (D7_2 + VDJ_D4_2)
BioProject PRJNA631246
SRA SRP260808

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE150140_RAW.tar 468.6 Mb (http)(custom) TAR (of CSV, H5, TAR)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap