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 naïve 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.