Table_6_Myocardial B cells have specific gene expression and predicted interactions in dilated cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy.xlsx

IntroductionGrowing evidence from animal models indicates that the myocardium hosts a population of B cells that play a role in the development of cardiomyopathy. However, there is minimal data on human myocardial B cells in the context of cardiomyopathy.
MethodsWe integrated single-cell and single-nuclei datasets from 45 healthy human hearts, 70 hearts with dilated cardiomyopathy (DCM), and 8 hearts with arrhythmogenic right ventricular cardiomyopathy (ARVC). Interactions between B cells and other cell types were investigated using the CellChat Package. Differential gene expression analysis comparing B cells across conditions was performed using DESeq2. Pathway analysis was performed using Ingenuity, KEGG, and GO pathways analysis.
ResultsWe identified 1,100 B cells, including naive B cells and plasma cells. Cells showed an extensive network of interactions within the healthy myocardium that included outgoing signaling to macrophages, T cells, endothelial cells, and pericytes, and incoming signaling from endothelial cells, pericytes, and fibroblasts. This niche relied on ECM-receptor, contact, and paracrine interactions; and changed significantly in the context of cardiomyopathy, displaying disease-specific features. Differential gene expression analysis showed that in the context of DCM both naive and plasma B cells upregulated several pathways related to immune activation, including upregulation of oxidative phosphorylation, upregulation of leukocyte extravasation, and, in naive B cells, antigen presentation.
DiscussionThe human myocardium contains naive B cells and plasma cells, integrated into a diverse and dynamic niche that has distinctive features in healthy, DCM, and ARVC. Naive myocardial-associated B cells likely contribute to the pathogenesis of human DCM.

引言 越来越多的动物模型研究证据表明，心肌组织中存在一类B细胞，其在心肌病的发生发展中发挥作用。然而，目前关于心肌病背景下人类心肌B细胞的相关研究数据仍十分有限。
方法 本研究整合了来自45例健康人类心脏、70例扩张型心肌病（dilated cardiomyopathy, DCM）患者心脏以及8例致心律失常性右室心肌病（arrhythmogenic right ventricular cardiomyopathy, ARVC）患者心脏的单细胞及单细胞核数据集。采用CellChat工具包分析B细胞与其他细胞类型之间的相互作用；使用DESeq2对不同分组的B细胞进行差异基因表达分析；通过Ingenuity、京都基因与基因组百科全书（Kyoto Encyclopedia of Genes and Genomes, KEGG）及基因本体（Gene Ontology, GO）通路分析开展通路富集分析。
结果 本研究共鉴定得到1100个B细胞，包括初始B细胞（naive B cell）和浆细胞。在健康心肌组织中，B细胞构成了广泛的细胞互作网络：可向巨噬细胞、T细胞、内皮细胞及周细胞发送信号，同时接收来自内皮细胞、周细胞和成纤维细胞的信号。该细胞微环境依赖于细胞外基质（extracellular matrix, ECM）-受体互作、细胞接触及旁分泌信号，并在心肌病背景下发生显著改变，呈现疾病特异性特征。差异基因表达分析显示，在扩张型心肌病背景下，初始B细胞与浆细胞均上调了多条与免疫激活相关的通路，包括氧化磷酸化通路上调、白细胞外渗通路上调，且初始B细胞还出现了抗原呈递相关通路的上调。
讨论 人类心肌组织中存在初始B细胞与浆细胞，它们整合形成一个多样化且动态变化的细胞微环境，该微环境在健康状态、扩张型心肌病及致心律失常性右室心肌病中具有各自独特的特征。心肌相关的初始B细胞可能参与人类扩张型心肌病的发病过程。