Bhalodia, A. | bioRxiv Science

bioRxiv2024

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

The cardio-splenic axis is a promising therapeutic target in ischemic heart failure (HF), but splenic-cardiac interactions after myocardial infarction (MI) are poorly understood. Here, we show that splenic follicular B cells drive ischemic HF via MHC class II-mediated antigen presentation. Transfer of splenic B cells from mice with ischemic HF induced adverse cardiac remodeling and modulated myocardial T-cells in naive recipients. Single-cell RNA sequencing of mouse and human post-MI B cells revealed upregulation of antigen-presentation related pathways. Mass spectrometry of the MHC II peptidome demonstrated enrichment of cardiac-derived peptides in MHC II molecules of splenic B cells from ischemic HF mice. B cell-specific deletion of MHC II suppressed adverse cardiac remodeling after adoptive transfer of post-MI splenic B cells. These results broaden our understanding of B-lymphocyte biology and point towards MHC II-mediated signaling in B-cells as a novel therapeutic target in ischemic HF.

immunology↗

bioRxiv2023

B cells occupy a unique, dynamic, biological niche within the human myocardium

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. 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 niche relied on ECM-receptor, contact, and paracrine interaction; 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 myocardium, DCM, and ARVC. Naive myocardial-associated B cells likely contribute to the pathogenesis of human DCM.

immunology↗