B cells promote atrial fibrillation via autoantibodies

Year: 2025

Type: article

Abstract: Atrial fibrillation, the most frequent cardiac arrhythmia, causes heart failure and stroke. Here we describe that combining the typical risk factors of atrial fibrillation (hypertension, obesity and mitral valve regurgitation (HOMER)) activates adaptive immunity in wild-type mice, ultimately causing electrical remodeling of cardiomyocytes. In HOMER mice, dendritic cells expanded in the left atria and heart-draining lymph nodes, where we detected cardiomyocyte-derived proteins. Systemically expanding B cells, while exposed to interferon-α, produced autoantibodies that disrupted calcium handling in cardiomyocytes. Depleting B cells by using μMT HOMER mice or plasma cells by using Mb1cre/+ Prdm1fl/fl HOMER mice reduced atrial fibrillation while mitigating the prolonged action potential duration we observed in the left atria of HOMER mice. CD20 antibody B cell depletion, a clinical tool in treating lymphoma and autoimmune disease, reduced atrial fibrillation fivefold in HOMER mice. Targeting humoral immunity may provide therapeutic avenues for patients with autoantibody-induced atrial fibrillation. Yamazoe et al. show that B cell-derived autoantibodies contribute to the development of atrial fibrillation, suggesting that targeting the humoral immune response may represent a viable therapeutic approach.

Source: Nature Cardiovascular Research

DOI: 10.1038/s44161-025-00724-z

Institutions: Harvard University, Massachusetts General Hospital, Center for Systems Biology, British Heart Foundation, University of Oxford, Broad Institute, University of Würzburg, Universitätsklinikum Würzburg, Icahn School of Medicine at Mount Sinai, University Hospital Regensburg

Language: English

Topic: Cardiac electrophysiology and arrhythmias

Subfield: Cardiology and Cardiovascular Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $12,690

Funders: U.S. Department of Health and Human Services, British Heart Foundation, National Institutes of Health, National Heart, Lung, and Blood Institute, National Cancer Institute, National Institute of Diabetes and Digestive and Kidney Diseases

Awards: G109265861, G1603729399, G170437431, G1740655365, Bone Marrow Endothelial VEGFR3 Regulation of Leukocyte Trafficking in Myocardial Infarction, G2848598751, G3643775926, G3763011920, G4405986302, G475755283, G5088351700, G5623424142, The BHF Chair of Cardiovascular Medicine, WNT Signaling in the Pathogenesis of Atrial Fibrillation, Macrophage heterogeneity in atrial remodeling, Macrophages in Cardiovascular Health, G97437508

OpenAlex ID: W4414930718