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Developmental changes in myocardial B cells mirror changes in B cells associated with different organs
Cibele Rocha-Resende, Wei Yang, Wenjun Li, Daniel Kreisel, Luigi Adamo, Douglas L. Mann
Cibele Rocha-Resende, Wei Yang, Wenjun Li, Daniel Kreisel, Luigi Adamo, Douglas L. Mann
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Research Article Cardiology Immunology

Developmental changes in myocardial B cells mirror changes in B cells associated with different organs

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Abstract

The naive heart harbors a population of intravascular B cells that make close contact with the cardiac microvasculature. However, the timing of their appearance and their organ specificity remain unknown. To address this knowledge gap, we performed a systematic analysis of B cells isolated from the myocardium and other organs, from embryonic life to adulthood. We found that the phenotype of myocardial B cells changed dynamically during development. While neonatal heart B cells were mostly CD11b+ and CD11b– CD21–CD23–, adult B cells were predominantly CD11b–CD21+CD23+. Histological analysis and intravital microscopy of lung and liver showed that organ-associated B cells in contact with the microvascular endothelium were not specific to the heart. Flow cytometric analysis of perfused hearts, livers, lungs, and spleen showed that the dynamic changes in B cell subpopulations observed in the heart during development mirrored changes observed in the other organs. Single cell RNA sequencing (scRNAseq) analysis of B cells showed that myocardial B cells were part of a larger population of organ-associated B cells that had a distinct transcriptional profile. These findings broaden our understanding of the biology of myocardial-associated B cells and suggest that current models of the dynamics of naive B cells during development are incomplete.

Authors

Cibele Rocha-Resende, Wei Yang, Wenjun Li, Daniel Kreisel, Luigi Adamo, Douglas L. Mann

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Figure 7

Myocardial-associated B cells are part of a pool of organ-associated B cells transcriptionally distinct from circulating B cells.

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Myocardial-associated B cells are part of a pool of organ-associated B c...
(A) UMAP plot of CD19+ cells sorted from the blood and from perfused heart, liver, and lung. B cells from different tissues were collected from the same mice. Unsupervised clustering analysis reveals that all identified clusters were present in all tissues analyzed. However, the prevalence of specific clusters varied. Cluster 0 is abundant in heart, liver, and lung and almost absent from circulating blood. Cluster 2 is highly prevalent in the blood and is rare in tissues. (B) Heatmap of the differentially expressed genes in blood, heart, liver, and lung. Transcriptional profile of blood cells is distinct from that of organ-associated B cells. (C) Heatmap of the differentially expressed genes in cluster 0. B cells in cluster 0 present a characteristic transcriptional signature when compared with the other clusters.

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