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However, the role of B cells in cardiomyocyte proliferation and heart regeneration has not been clarified. Here, we found that the neonatal mice with B cell depletion showed markedly reduced cardiomyocyte proliferation, leading to cardiac dysfunction, fibrosis scar formation, and the complete failure of heart regeneration after apical resection. B cell depletion also significantly impaired heart regeneration and cardiac function in neonatal mice following myocardial infarction (MI). However, B cell depletion in adult mice suppressed tissue inflammation, inhibited myocardial fibrosis, and improved cardiac function after MI. Interestingly, B cell depletion partially restricted cardiomyocyte proliferation in adult mice post-MI. Single-cell RNA sequencing showed that cardiac B cells possessed a more powerful ability to inhibit inflammatory responses and enhance angiogenesis in the postnatal day 1 (P1) mice compared with P7 and adult mice. Besides, the proportion of cardioprotective B cell clusters with high expression levels of <jats:italic>S100a6<\/jats:italic> (S100 calcium-binding protein A6) and <jats:italic>S100a4<\/jats:italic> (S100 calcium-binding protein A4) was greatly decreased in adult heart tissues compared with neonatal mice after cardiac damage. Thus, our study discovers that cardiac B cells in neonatal mice are required for cardiomyocyte proliferation and heart regeneration, while adult B cells promote inflammation and impair cardiac function after myocardial injury.<\/jats:p>","DOI":"10.1038\/s41536-023-00282-7","type":"journal-article","created":{"date-parts":[[2023,2,11]],"date-time":"2023-02-11T08:02:51Z","timestamp":1676102571000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Murine neonatal cardiac B cells promote cardiomyocyte proliferation and heart regeneration"],"prefix":"10.1038","volume":"8","author":[{"given":"Yong","family":"Tan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuewen","family":"Duan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9474-0274","authenticated-orcid":false,"given":"Bo","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1928-8847","authenticated-orcid":false,"given":"Xingguang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4943-1659","authenticated-orcid":false,"given":"Zhenzhen","family":"Zhan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,2,11]]},"reference":[{"key":"282_CR1","doi-asserted-by":"publisher","first-page":"1078","DOI":"10.1126\/science.1200708","volume":"331","author":"ER Porrello","year":"2011","unstructured":"Porrello, E. 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