Dissecting antibody responses to cardiac receptors in patients with myocardial infarction
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Myocardial infarction (MI) triggers the production of heart-reactive serum antibodies, but their antigen specificities and impact on cardiomyocyte function remain poorly understood. Using single-cell RNA and B cell receptor sequencing (scRNA/BCRseq) on plasmablasts isolated from patients with MI combined with antibody engineering, we identified B cell clones expanded in response to MI, and generated a panel of 17 recombinant monoclonal antibodies having the same binding domains as those identified in patients scBCR datasets (MI-mAb). This approach enabled us to map antibody specificities and dissect their functional impact on cardiomyocytes. Our findings reveal that post-MI B cell responses target cardiac receptors, including extracellular epitopes mapped to beta adrenergic receptors (β-ARs). Notably, some of the β-AR-specific MI-mAbs induced intracellular cAMP signaling and ultimately modulated cardiomyocyte excitation-contraction coupling. Taken together, these observations provide mechanistic evidence for expanding B cells in the context of MI, with the production of antibodies targeting cardiac receptors that can impact myocardial pathophysiology.
