Center for Cardiovascular Research, Cardiovascular Division, Department of Medicine.
Genome Technology Access Center, Department of Genetics.
JCI Insight. 2020 Aug 20;5(16):139377. doi: 10.1172/jci.insight.139377.
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.
幼稚的心脏中存在一群血管内 B 细胞，它们与心脏微血管密切接触。然而，它们的出现时间和器官特异性仍不清楚。为了填补这一知识空白，我们对从胚胎期到成年期从心肌和其他器官中分离出的 B 细胞进行了系统分析。我们发现，心肌 B 细胞的表型在发育过程中发生了动态变化。虽然新生儿心脏 B 细胞主要为 CD11b+和 CD11b-CD21-CD23-，但成年 B 细胞主要为 CD11b-CD21+CD23+。对肺和肝的组织学分析和活体显微镜检查表明，与微血管内皮接触的器官相关 B 细胞并非心脏所特有。对灌注心脏、肝脏、肺和脾脏的流式细胞术分析表明，在发育过程中观察到心脏中 B 细胞亚群的动态变化与在其他器官中观察到的变化相吻合。B 细胞的单细胞 RNA 测序 (scRNAseq) 分析表明，心肌 B 细胞是具有独特转录特征的更大的器官相关 B 细胞群体的一部分。这些发现拓宽了我们对心肌相关 B 细胞生物学的理解，并表明目前关于发育过程中幼稚 B 细胞动态的模型不完整。
