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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 5

Changes in myocardial-associated B cell subsets mirror changes in B cell subsets observed in spleen, blood, lung, and liver, despite the presence of organ-specific features.

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Changes in myocardial-associated B cell subsets mirror changes in B cell...
(A) Group data showing the composition B cell in the heart, spleen, blood, lung, and liver from P1 to 5 weeks of age. B cell composition is similar in all tissues and goes through the same dynamic changes during growth. The IgMhiCD5+ subset expands in early neonatal life, and the CD21–CD23– subset gradually decreases during development as the prevalence of the CD21+CD23+ subset increases. (B) Summary data showing the contribution of each B cell subset across tissues at different time points during growth. Despite marked similarities, tissue-specific features are present at various time points. Supplemental Table 4 shows the statistical analysis of each tissue and subset. n = 4–6 samples/condition. At P1, tissues from 3–4 animals were pooled together to constitute n = 1.

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