Myocardial B cells have specific gene expression and predicted interactions in Dilated Cardiomyopathy and Arrhythmogenic Right Ventricular Cardiomyopathy

Abstract

Background: A growing body of 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 and their biological niche within the heart remains mostly unexplored. Methods: We 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. Results: Out of 1,200,752 nuclei and 49,723 cells, we identified 1,100 B cells, including naive B cells and plasma cells. B 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 biological niche relied on both ECM-receptor interactions, cell-cell contact interactions, and paracrine interaction, it changed significantly in the context of cardiomyopathy and had disease-specific features. Differential gene expression analysis showed that in the context of DCM both naive and plasma myocardial B cells upregulated several pathways related to immune activation, including upregulation of oxidative phosphorylation, upregulation of leukocyte extravasation and, in naive B cells, antigen processing and presentation. Conclusions: The human healthy and diseased myocardium contains naive B cells and plasma cells, integrated in a diverse and dynamic biological niche. Naive myocardial-associated B cells likely contribute to the pathogenesis of human dilated cardiomyopathy.

B cell-mediated antigen presentation promotes adverse cardiac remodeling in chronic heart failure

“…A clustering resolution of 0.5 and 0.4 was used for the ICM and STEMI datasets respectively. B cells were identified using known human B cell-specific makers as previously described (Supplementary Table 5) (43). Subsequent comparative gene analyses and pathway analyses were performed as described above.…”