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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 1

Myocardial B cell subsets change from late embryonic life to adulthood.

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Myocardial B cell subsets change from late embryonic life to adulthood.
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(A) Representative flow charts showing the expression of CD5 and IgM in CD19+CD11b+ B cells in the heart from E13.5 to 10 weeks of age. The box inserts within each graph delineate the positions of the IgMhiCD5+ subset and of the IgMhiCD5– subset. The prevalence of IgMhiCD5+ B cells increases during neonatal life (peak at P7), but this is not sustained during adult life. (B) Representative flow charts of CD21 and CD23 expression in myocardial CD19+CD11b– B cells. The box inserts within each graph delineate CD21–CD23– and CD21+CD23+ subsets. CD21–CD23– cells are the majority of B cells at birth, and their prevalence gradually decreases as the prevalence of CD21+CD23+ increases. CD21+CD23+ constitute the major B cell subgroup in the adult naive heart. (C) Summary graph showing the dynamic changes in B cell composition from embryonic to adult life in the heart. n = 4–7 samples. Supplemental Table 1 shows the statistical analysis of each subset from embryonic through adult life. From E13.5 to P7, 3–6 embryonic and neonatal hearts were pooled together to constitute n = 1.

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