The human myocardium harbors a population of naive B-cells with a distinctive gene expression signature conserved across species
IntroductionCardiac immunology studies in murine models have identified a sizeable population of myocardial B-cells and have shown that its modulation represents a promising strategy to develop novel therapies for heart failure. However, scarce data on B-cells in the human heart leaves unclear wheth...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-09-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.973211/full |
| _version_ | 1797997544082505728 |
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| author | Kevin C. Bermea Nicolas Kostelecky Sylvie T. Rousseau Chieh-Yu Lin Luigi Adamo |
| author_facet | Kevin C. Bermea Nicolas Kostelecky Sylvie T. Rousseau Chieh-Yu Lin Luigi Adamo |
| author_sort | Kevin C. Bermea |
| collection | DOAJ |
| description | IntroductionCardiac immunology studies in murine models have identified a sizeable population of myocardial B-cells and have shown that its modulation represents a promising strategy to develop novel therapies for heart failure. However, scarce data on B-cells in the human heart leaves unclear whether findings in rodents are relevant to human biology.MethodsWe performed immunohistochemical stains to characterize the amount and distribution of B-cells in human hearts, analyzing both fresh and post-mortem tissue. To gain insight into the biology of human myocardial B-cells we analyzed publicly-available spatial transcriptomics and single-cell sequencing datasets of myocardial and peripheral blood mononuclear cells (PBMCs). We validated these findings on primary B-cells sorted from the heart and peripheral blood of left ventricular assistive device recipients. To identify biological pathways upregulated in myocardial B-cells across species, we compared differential gene expression in myocardial vs peripheral blood B-cells across the studied human datasets and published rodent datasets.ResultsIn healthy human heart samples, we found B-cells at a ratio of 1:8 compared to T-cells (2.41 ± 0.45 vs 19.36 ± 4.43, p-value <0.001). Myocardial B-cells were more abundant in the interstitium compared with the intravascular space (p-value=0.011), and also more abundant in the myocardium vs. epicardium (p-value=0.048). Single-cell gene expression analysis showed that the human myocardium harbored mostly naive B-cells with a gene expression profile distinct from that of PBMC B-cells. Cross-comparison of differentially-expressed genes in myocardial vs. PBMC B-cells across human and rodent datasets identified 703 genes with consistent differential gene expression across species (binomial p-value=2.9e-48). KEGG pathway analysis highlighted “B-cell receptor signaling pathway,” “Antigen processing and presentation,” and “Cytokine-cytokine receptor interaction” among the top pathways upregulated in cardiac B-cells (FDR <0.001) conserved between species.ConclusionsLike the murine heart, the human heart harbors naive B-cells that are both intravascular and extravascular. Human myocardial B-cells are fewer and more evenly distributed between these two compartments than rodent myocardial B-cells. However, analysis of single-gene expression data indicates that the biological function of myocardial B-cells is conserved across species. |
| first_indexed | 2024-04-11T10:33:26Z |
| format | Article |
| id | doaj.art-2b1a252758f247c3ba38a152532ff328 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-11T10:33:26Z |
| publishDate | 2022-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-2b1a252758f247c3ba38a152532ff3282022-12-22T04:29:21ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-09-011310.3389/fimmu.2022.973211973211The human myocardium harbors a population of naive B-cells with a distinctive gene expression signature conserved across speciesKevin C. Bermea0Nicolas Kostelecky1Sylvie T. Rousseau2Chieh-Yu Lin3Luigi Adamo4Division of Cardiology, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, United StatesDepartment of Pathology, Washington University in St. Louis School of Medicine, St. Louis, MO, United StatesDivision of Cardiology, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, United StatesDepartment of Pathology, Washington University in St. Louis School of Medicine, St. Louis, MO, United StatesDivision of Cardiology, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, United StatesIntroductionCardiac immunology studies in murine models have identified a sizeable population of myocardial B-cells and have shown that its modulation represents a promising strategy to develop novel therapies for heart failure. However, scarce data on B-cells in the human heart leaves unclear whether findings in rodents are relevant to human biology.MethodsWe performed immunohistochemical stains to characterize the amount and distribution of B-cells in human hearts, analyzing both fresh and post-mortem tissue. To gain insight into the biology of human myocardial B-cells we analyzed publicly-available spatial transcriptomics and single-cell sequencing datasets of myocardial and peripheral blood mononuclear cells (PBMCs). We validated these findings on primary B-cells sorted from the heart and peripheral blood of left ventricular assistive device recipients. To identify biological pathways upregulated in myocardial B-cells across species, we compared differential gene expression in myocardial vs peripheral blood B-cells across the studied human datasets and published rodent datasets.ResultsIn healthy human heart samples, we found B-cells at a ratio of 1:8 compared to T-cells (2.41 ± 0.45 vs 19.36 ± 4.43, p-value <0.001). Myocardial B-cells were more abundant in the interstitium compared with the intravascular space (p-value=0.011), and also more abundant in the myocardium vs. epicardium (p-value=0.048). Single-cell gene expression analysis showed that the human myocardium harbored mostly naive B-cells with a gene expression profile distinct from that of PBMC B-cells. Cross-comparison of differentially-expressed genes in myocardial vs. PBMC B-cells across human and rodent datasets identified 703 genes with consistent differential gene expression across species (binomial p-value=2.9e-48). KEGG pathway analysis highlighted “B-cell receptor signaling pathway,” “Antigen processing and presentation,” and “Cytokine-cytokine receptor interaction” among the top pathways upregulated in cardiac B-cells (FDR <0.001) conserved between species.ConclusionsLike the murine heart, the human heart harbors naive B-cells that are both intravascular and extravascular. Human myocardial B-cells are fewer and more evenly distributed between these two compartments than rodent myocardial B-cells. However, analysis of single-gene expression data indicates that the biological function of myocardial B-cells is conserved across species.https://www.frontiersin.org/articles/10.3389/fimmu.2022.973211/fullB-cellsheartcardiologycardiac immunologycardiac inflammationnaive B-cells |
| spellingShingle | Kevin C. Bermea Nicolas Kostelecky Sylvie T. Rousseau Chieh-Yu Lin Luigi Adamo The human myocardium harbors a population of naive B-cells with a distinctive gene expression signature conserved across species Frontiers in Immunology B-cells heart cardiology cardiac immunology cardiac inflammation naive B-cells |
| title | The human myocardium harbors a population of naive B-cells with a distinctive gene expression signature conserved across species |
| title_full | The human myocardium harbors a population of naive B-cells with a distinctive gene expression signature conserved across species |
| title_fullStr | The human myocardium harbors a population of naive B-cells with a distinctive gene expression signature conserved across species |
| title_full_unstemmed | The human myocardium harbors a population of naive B-cells with a distinctive gene expression signature conserved across species |
| title_short | The human myocardium harbors a population of naive B-cells with a distinctive gene expression signature conserved across species |
| title_sort | human myocardium harbors a population of naive b cells with a distinctive gene expression signature conserved across species |
| topic | B-cells heart cardiology cardiac immunology cardiac inflammation naive B-cells |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.973211/full |
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