{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T20:04:33Z","timestamp":1776542673801,"version":"3.51.2"},"posted":{"date-parts":[[2023,9,23]]},"group-title":"Immunology","reference-count":76,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,1,16]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:sec>\n                  <jats:title>Introduction<\/jats:title>\n                  <jats:p>Growing 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.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We 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.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We 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.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Discussion<\/jats:title>\n                  <jats:p>The 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.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2023.09.21.558902","type":"posted-content","created":{"date-parts":[[2023,9,23]],"date-time":"2023-09-23T18:40:10Z","timestamp":1695494410000},"source":"Crossref","is-referenced-by-count":1,"title":["Myocardial B cells have specific gene expression and predicted interactions in Dilated Cardiomyopathy and Arrhythmogenic Right Ventricular Cardiomyopathy"],"prefix":"10.64898","author":[{"given":"Kevin C.","family":"Bermea","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carolina","family":"Duque","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charles D.","family":"Cohen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aashik","family":"Bhalodia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sylvie","family":"Rousseau","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jana","family":"Lovell","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcelle Dina","family":"Zita","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1535-2530","authenticated-orcid":false,"given":"Monica R.","family":"Mugnier","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2704-978X","authenticated-orcid":false,"given":"Luigi","family":"Adamo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2024011906400761000_2023.09.21.558902v2.1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.2200924"},{"issue":"1","key":"2024011906400761000_2023.09.21.558902v2.2","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1038\/s41572-019-0084-1","article-title":"Dilated cardiomyopathy","volume":"5","year":"2019","journal-title":"Nat Rev Dis Primers"},{"key":"2024011906400761000_2023.09.21.558902v2.3","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.121.055890"},{"issue":"5","key":"2024011906400761000_2023.09.21.558902v2.4","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1038\/s41569-019-0315-x","article-title":"Reappraising the role of inflammation in heart failure","volume":"17","year":"2020","journal-title":"Nat Rev Cardiol"},{"key":"2024011906400761000_2023.09.21.558902v2.5","doi-asserted-by":"publisher","DOI":"10.1007\/s11886-022-01722-4"},{"key":"2024011906400761000_2023.09.21.558902v2.6","doi-asserted-by":"crossref","unstructured":"Adamo L , Rocha-Resende C , Lin CY , Evans S , Williams J , Dun H , et al. Myocardial B cells are a subset of circulating lymphocytes with delayed transit through the heart. JCI Insight. 2020;5(3).","DOI":"10.1172\/jci.insight.134700"},{"key":"2024011906400761000_2023.09.21.558902v2.7","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0034730"},{"key":"2024011906400761000_2023.09.21.558902v2.8","doi-asserted-by":"crossref","unstructured":"Rocha-Resende C , Yang W , Li W , Kreisel D , Adamo L , Mann DL . Developmental changes in myocardial B cells mirror changes in B cells associated with different organs. JCI Insight. 2020;5(16).","DOI":"10.1172\/jci.insight.139377"},{"key":"2024011906400761000_2023.09.21.558902v2.9","doi-asserted-by":"crossref","unstructured":"Bermea KC , Kostelecky N , Rousseau ST , Lin C-Y , Adamo L . The human myocardium harbors a population of naive B-cells with a distinctive gene expression signature conserved across species. Frontiers in Immunology. 2022;13.","DOI":"10.3389\/fimmu.2022.973211"},{"key":"2024011906400761000_2023.09.21.558902v2.10","doi-asserted-by":"crossref","unstructured":"Adamo L , Staloch LJ , Rocha-Resende C , Matkovich SJ , Jiang W , Bajpai G , et al. Modulation of subsets of cardiac B lymphocytes improves cardiac function after acute injury. JCI Insight. 2018;3(11).","DOI":"10.1172\/jci.insight.120137"},{"key":"2024011906400761000_2023.09.21.558902v2.11","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2021.05.003"},{"key":"2024011906400761000_2023.09.21.558902v2.12","doi-asserted-by":"crossref","unstructured":"Cordero-Reyes AM , Youker KA , Trevino AR , Celis R , Hamilton DJ , Flores-Arredondo JH , et al. Full Expression of Cardiomyopathy Is Partly Dependent on B-Cells: A Pathway That Involves Cytokine Activation, Immunoglobulin Deposition, and Activation of Apoptosis. J Am Heart Assoc. 2016;5(1).","DOI":"10.1161\/JAHA.115.002484"},{"key":"2024011906400761000_2023.09.21.558902v2.13","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2021.11.051"},{"key":"2024011906400761000_2023.09.21.558902v2.14","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3284"},{"key":"2024011906400761000_2023.09.21.558902v2.15","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvab181"},{"key":"2024011906400761000_2023.09.21.558902v2.16","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1911464116"},{"key":"2024011906400761000_2023.09.21.558902v2.17","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.94.5.983"},{"key":"2024011906400761000_2023.09.21.558902v2.18","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.97.16.1571"},{"key":"2024011906400761000_2023.09.21.558902v2.19","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2020.06.005"},{"key":"2024011906400761000_2023.09.21.558902v2.20","doi-asserted-by":"publisher","DOI":"10.1038\/ncpcardio1182"},{"key":"2024011906400761000_2023.09.21.558902v2.21","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-20450-w"},{"issue":"3","key":"2024011906400761000_2023.09.21.558902v2.22","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1038\/s44161-022-00028-6","article-title":"Single-cell transcriptomics reveals cell-type-specific diversification in human heart failure","volume":"1","year":"2022","journal-title":"Nature Cardiovascular Research"},{"key":"2024011906400761000_2023.09.21.558902v2.23","doi-asserted-by":"publisher","DOI":"10.1126\/science.abo1984"},{"key":"2024011906400761000_2023.09.21.558902v2.24","unstructured":"R core team. R: A language and environment for statistical computing. Vienna, Austria: R Foundation for Statistical Computing; 2021."},{"key":"2024011906400761000_2023.09.21.558902v2.25","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.3192"},{"key":"2024011906400761000_2023.09.21.558902v2.26","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.4096"},{"issue":"13","key":"2024011906400761000_2023.09.21.558902v2.27","first-page":"3573","article-title":"3rd, Zheng S, Butler A","volume":"184","year":"2021","journal-title":"Integrated analysis of multimodal single-cell data. Cell"},{"issue":"7","key":"2024011906400761000_2023.09.21.558902v2.28","first-page":"1888","article-title":"3rd","volume":"177","year":"2019","journal-title":"Comprehensive Integration of Single-Cell Data. Cell"},{"key":"2024011906400761000_2023.09.21.558902v2.29","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2009.97"},{"key":"2024011906400761000_2023.09.21.558902v2.30","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-28803-w"},{"key":"2024011906400761000_2023.09.21.558902v2.31","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkac947"},{"key":"2024011906400761000_2023.09.21.558902v2.32","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btt703"},{"key":"2024011906400761000_2023.09.21.558902v2.33","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-019-1874-1"},{"key":"2024011906400761000_2023.09.21.558902v2.34","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-021-02584-9"},{"issue":"1","key":"2024011906400761000_2023.09.21.558902v2.35","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1038\/s41467-021-21246-9","article-title":"Inference and analysis of cell-cell communication using CellChat","volume":"12","year":"2021","journal-title":"Nat Commun"},{"key":"2024011906400761000_2023.09.21.558902v2.36","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.121.316668"},{"key":"2024011906400761000_2023.09.21.558902v2.37","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1004"},{"key":"2024011906400761000_2023.09.21.558902v2.38","doi-asserted-by":"publisher","DOI":"10.2174\/1389557515666150203144111"},{"key":"2024011906400761000_2023.09.21.558902v2.39","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1302209"},{"key":"2024011906400761000_2023.09.21.558902v2.40","first-page":"1049143","article-title":"The role of CD74 in cardiovascular disease","volume":"9","year":"2022","journal-title":"Front Cardiovasc Med"},{"key":"2024011906400761000_2023.09.21.558902v2.41","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2020.102575"},{"issue":"1","key":"2024011906400761000_2023.09.21.558902v2.42","doi-asserted-by":"crossref","first-page":"3287","DOI":"10.1038\/s41467-018-05770-9","article-title":"Galectin-9 suppresses B cell receptor signaling and is regulated by I-branching of N-glycans","volume":"9","year":"2018","journal-title":"Nat Commun"},{"key":"2024011906400761000_2023.09.21.558902v2.43","doi-asserted-by":"crossref","first-page":"973211","DOI":"10.3389\/fimmu.2022.973211","article-title":"The human myocardium harbors a population of naive B-cells with a distinctive gene expression signature conserved across species","volume":"13","year":"2022","journal-title":"Front Immunol"},{"key":"2024011906400761000_2023.09.21.558902v2.44","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06311-1"},{"key":"2024011906400761000_2023.09.21.558902v2.45","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E06-04-0320"},{"key":"2024011906400761000_2023.09.21.558902v2.46","doi-asserted-by":"crossref","unstructured":"Bellan M , Pirisi M , Sainaghi PP . The Gas6\/TAM System and Multiple Sclerosis. Int J Mol Sci. 2016;17(11).","DOI":"10.3390\/ijms17111807"},{"key":"2024011906400761000_2023.09.21.558902v2.47","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.107.151456"},{"key":"2024011906400761000_2023.09.21.558902v2.48","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.84752"},{"key":"2024011906400761000_2023.09.21.558902v2.49","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2021.1885183"},{"key":"2024011906400761000_2023.09.21.558902v2.50","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0110062"},{"key":"2024011906400761000_2023.09.21.558902v2.51","doi-asserted-by":"publisher","DOI":"10.1080\/10409238.2016.1215288"},{"key":"2024011906400761000_2023.09.21.558902v2.52","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-013-9889-y"},{"key":"2024011906400761000_2023.09.21.558902v2.53","doi-asserted-by":"crossref","unstructured":"Bermea K , Bhalodia A , Huff A , Rousseau S , Adamo L . The Role of B Cells in Cardiomyopathy and Heart Failure. Curr Cardiol Rep. 2022.","DOI":"10.1007\/s11886-022-01722-4"},{"key":"2024011906400761000_2023.09.21.558902v2.54","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.117.028833"},{"key":"2024011906400761000_2023.09.21.558902v2.55","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-2776(08)60537-4"},{"key":"2024011906400761000_2023.09.21.558902v2.56","doi-asserted-by":"publisher","DOI":"10.1126\/science.278.5338.672"},{"key":"2024011906400761000_2023.09.21.558902v2.57","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2015.00182"},{"key":"2024011906400761000_2023.09.21.558902v2.58","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-06-1837"},{"key":"2024011906400761000_2023.09.21.558902v2.59","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-042617-053104"},{"key":"2024011906400761000_2023.09.21.558902v2.60","doi-asserted-by":"crossref","unstructured":"Horckmans M , Bianchini M , Santovito D , Megens RTA , Springael JY , Negri I , et al. Pericardial Adipose Tissue Regulates Granulopoiesis, Fibrosis and Cardiac Function After Myocardial Infarction. Circulation. 2017.","DOI":"10.1161\/CIRCULATIONAHA.117.028833"},{"key":"2024011906400761000_2023.09.21.558902v2.61","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.15.2855"},{"key":"2024011906400761000_2023.09.21.558902v2.62","doi-asserted-by":"publisher","DOI":"10.1084\/jem.173.6.1521"},{"key":"2024011906400761000_2023.09.21.558902v2.63","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2017.09.023"},{"key":"2024011906400761000_2023.09.21.558902v2.64","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20161702"},{"key":"2024011906400761000_2023.09.21.558902v2.65","doi-asserted-by":"crossref","unstructured":"Sava P , Ramanathan A , Dobronyi A , Peng X , Sun H , Ledesma-Mendoza A , et al. Human pericytes adopt myofibroblast properties in the microenvironment of the IPF lung. JCI Insight. 2017;2(24).","DOI":"10.1172\/jci.insight.96352"},{"key":"2024011906400761000_2023.09.21.558902v2.66","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2008.080433"},{"key":"2024011906400761000_2023.09.21.558902v2.67","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201212-2297OC"},{"key":"2024011906400761000_2023.09.21.558902v2.68","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.119.045115"},{"key":"2024011906400761000_2023.09.21.558902v2.69","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.64.1.97"},{"key":"2024011906400761000_2023.09.21.558902v2.70","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(02)02075-2"},{"issue":"4","key":"2024011906400761000_2023.09.21.558902v2.71","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1002\/ehf2.12744","article-title":"The role of B cells in heart failure and implications for future immunomodulatory treatment strategies","volume":"7","year":"2020","journal-title":"ESC Heart Fail"},{"key":"2024011906400761000_2023.09.21.558902v2.72","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(01)01309-2"},{"key":"2024011906400761000_2023.09.21.558902v2.73","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200211283472220"},{"key":"2024011906400761000_2023.09.21.558902v2.74","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.101.4.385"},{"key":"2024011906400761000_2023.09.21.558902v2.75","doi-asserted-by":"crossref","unstructured":"Tsch\u00f6pe C , Van Linthout S , Spillmann F , Posch MG , Reinke P , Volk HD , et al. Targeting CD20+ B-lymphocytes in inflammatory dilated cardiomyopathy with rituximab improves clinical course: a case series. Eur Heart J Case Rep. 2019;3(3).","DOI":"10.1093\/ehjcr\/ytz131"},{"key":"2024011906400761000_2023.09.21.558902v2.76","unstructured":"Bermea KC , Duque C , Cohen CD , Bhalodia A , Rousseau S , Lovell J , et al. B cells occupy a unique, dynamic, biological niche within the human myocardium. bioRxiv. 2023:2023.09.21.558902."}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2023.09.21.558902","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T05:16:10Z","timestamp":1768454170000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2023.09.21.558902"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,23]]},"references-count":76,"URL":"https:\/\/doi.org\/10.1101\/2023.09.21.558902","relation":{"is-preprint-of":[{"id-type":"doi","id":"10.3389\/fimmu.2024.1327372","asserted-by":"subject"}]},"subject":[],"published":{"date-parts":[[2023,9,23]]},"subtype":"preprint"}}