Cardiovascular Division, Department of Medicine, and.
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.
JCI Insight. 2020 Feb 13;5(3):134700. doi: 10.1172/jci.insight.134700.
Current models of B lymphocyte biology posit that B cells continuously recirculate between lymphoid organs, without accumulating in peripheral healthy tissues. Nevertheless, B lymphocytes are one of the most prevalent leukocyte populations in the naive murine heart. To investigate this apparent inconsistency in the literature, we conducted a systematic analysis of myocardial B cell ontogeny, trafficking dynamics, histology, and gene expression patterns. We found that myocardial B cells represent a subpopulation of circulating B cells that make close contact with the microvascular endothelium of the heart and arrest their transit as they pass through the heart. The vast majority (>95%) of myocardial B cells remain intravascular, whereas few (<5%) myocardial B cells cross the endothelium into myocardial tissue. Analyses of mice with B cell deficiency or depletion indicated that B cells modulate the myocardial leukocyte pool composition. Analysis of B cell-deficient animals suggested that B cells modulate myocardial growth and contractility. These results transform our current understanding of B cell recirculation in the naive state and reveal a previously unknown relationship between B cells and myocardial physiology. Further work will be needed to assess the relevance of these findings to other organs.
当前的 B 淋巴细胞生物学模型假设 B 细胞在淋巴器官之间持续循环,而不会在周围健康组织中积累。然而,B 淋巴细胞是幼稚鼠心脏中最常见的白细胞群体之一。为了解决文献中的这一明显矛盾,我们对心肌 B 细胞发生、迁移动力学、组织学和基因表达模式进行了系统分析。我们发现,心肌 B 细胞代表循环 B 细胞的一个亚群,它们与心脏的微血管内皮密切接触,并在通过心脏时停止迁移。绝大多数(>95%)心肌 B 细胞保持在血管内,而只有少数(<5%)心肌 B 细胞穿过内皮进入心肌组织。对 B 细胞缺乏或耗竭的小鼠进行分析表明,B 细胞调节心肌白细胞池的组成。对 B 细胞缺陷动物的分析表明,B 细胞调节心肌的生长和收缩性。这些结果改变了我们对幼稚状态下 B 细胞再循环的现有认识,并揭示了 B 细胞与心肌生理学之间以前未知的关系。需要进一步的工作来评估这些发现与其他器官的相关性。