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

B cell-mediated antigen presentation promotes adverse cardiac remodeling in chronic heart failure | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Biological Sciences - Article B cell-mediated antigen presentation promotes adverse cardiac remodeling in chronic heart failure Luigi Adamo, Jana Lovell, Carolina Duque, Sylvie Rousseau, Aashik Bhalodia, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4536350/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Cardiovascular disease remains the leading cause of death worldwide. A primary driver of cardiovascular mortality is ischemic heart failure, a form of cardiac dysfunction that can develop in patients who survive myocardial infarction. Acute cardiac damage triggers robust changes in the spleen with rapid migration of immune cells from the spleen to the heart. Activating this “cardio-splenic” axis contributes to progressive cardiac dysfunction. The cardio-splenic axis has, therefore, been identified as a promising therapeutic target to prevent or treat heart failure. However, our understanding of the precise mechanisms by which specific immune cells contribute to adverse cardiac remodeling within the cardio-splenic axis remains limited. Here, we show that splenic B cells contribute to the development of heart failure via MHC II-mediated antigen presentation. We found that the adoptive transfer of splenic B cells from mice with ischemic heart failure promoted adverse cardiac remodeling and splenic inflammatory changes in naïve recipient mice. Based on single-cell RNA sequencing analysis of splenic B cells from mice with ischemic heart failure, we hypothesized that B cells contributed to adverse cardiac remodeling through antigen presentation by MHC II molecules. This mechanism was confirmed using transgenic mice with B cell-specific MHC II deletion, and by analyzing circulating B cells from humans who experienced myocardial infarction. Our results broaden our understanding of B lymphocyte biology, reshape current models of immune activation in response to myocardial injury, and point towards MHC II-mediated signaling in B cells as a novel and specific therapeutic target in chronic heart failure. Biological sciences/Immunology/Antigen processing and presentation/MHC/MHC class II Health sciences/Diseases/Cardiovascular diseases/Heart failure Biological sciences/Immunology/Lymphocytes/B cells Full Text Additional Declarations There is NO Competing Interest. Supplementary Files CSASupplementaryFigure1Nature.pdf Representative splenic B cell isolation for adoptive transfer studies MousescRNASequencingGSEA.xlsx Supplementary Table 1 PatientscRNASequencingGSEA.xlsx Supplementary Table 2 CSASupplementaryTable3Nature.pdf Supplementary Table 3 CSASupplementaryTable4Nature.pdf Supplementary Table 4 CSAExtendedDataNature.pdf Extended Data Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4536350","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Biological Sciences - Article","associatedPublications":[],"authors":[{"id":316316411,"identity":"da632ba5-84db-4c0e-b72f-245a4676dda6","order_by":0,"name":"Luigi 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A primary driver of cardiovascular mortality is ischemic heart failure, a form of cardiac dysfunction that can develop in patients who survive myocardial infarction. Acute cardiac damage triggers robust changes in the spleen with rapid migration of immune cells from the spleen to the heart. Activating this “cardio-splenic” axis contributes to progressive cardiac dysfunction. The cardio-splenic axis has, therefore, been identified as a promising therapeutic target to prevent or treat heart failure. However, our understanding of the precise mechanisms by which specific immune cells contribute to adverse cardiac remodeling within the cardio-splenic axis remains limited. Here, we show that splenic B cells contribute to the development of heart failure via MHC II-mediated antigen presentation. We found that the adoptive transfer of splenic B cells from mice with ischemic heart failure promoted adverse cardiac remodeling and splenic inflammatory changes in naïve recipient mice. Based on single-cell RNA sequencing analysis of splenic B cells from mice with ischemic heart failure, we hypothesized that B cells contributed to adverse cardiac remodeling through antigen presentation by MHC II molecules. This mechanism was confirmed using transgenic mice with B cell-specific MHC II deletion, and by analyzing circulating B cells from humans who experienced myocardial infarction. Our results broaden our understanding of B lymphocyte biology, reshape current models of immune activation in response to myocardial injury, and point towards MHC II-mediated signaling in B cells as a novel and specific therapeutic target in chronic heart failure.","manuscriptTitle":"B cell-mediated antigen presentation promotes adverse cardiac remodeling in chronic heart failure","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-06-24 02:21:58","doi":"10.21203/rs.3.rs-4536350/v1","editorialEvents":[],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"nature-cardiovascular-research","isNatureJournal":true,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"natcardiovascres","sideBox":"Learn more about [Nature Cardiovascular Research](https://www.nature.com/natcardiovascres/)","snPcode":"","submissionUrl":"https://mts-natcardiovascres.nature.com/cgi-bin/main.plex","title":"Nature Cardiovascular Research","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature Research","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"7445c282-0fd7-414e-8374-dea01f0330bb","owner":[],"postedDate":"June 24th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":33448829,"name":"Biological sciences/Immunology/Antigen processing and presentation/MHC/MHC class II"},{"id":33448830,"name":"Health sciences/Diseases/Cardiovascular diseases/Heart failure"},{"id":33448831,"name":"Biological sciences/Immunology/Lymphocytes/B cells"}],"tags":[],"updatedAt":"2026-04-27T19:05:17+00:00","versionOfRecord":[],"versionCreatedAt":"2024-06-24 02:21:58","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4536350","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4536350","identity":"rs-4536350","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}