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The CD5\n                    <jats:sup>+<\/jats:sup>\n                    B-1a subset expresses anti-inflammatory molecules including IL-10, PDL1 and CTLA4 and can be immunoregulatory\n                    <jats:sup>4\u20136<\/jats:sup>\n                    . Unlike conventional B cells that are continuously replenished, B-1a cells are produced early in life and maintained through self-renewal\n                    <jats:sup>7<\/jats:sup>\n                    . Here we show that the transcription factors TCF1 and LEF1 are critical regulators of B-1a cells. LEF1 expression is highest in fetal and bone marrow B-1 progenitors, whereas the levels of TCF1 are higher in splenic and peritoneal B-1 cells than in B-1 progenitors. TCF1\u2013LEF1 double deficient mice have reduced B-1a cells and defective B-1a cell maintenance. These transcription factors promote MYC-dependent metabolic pathways and induce a stem-like population upon activation, partly via IL-10 production. In the absence of TCF1 and LEF1, B-1 cells proliferate excessively and acquire an exhausted phenotype with reduced IL-10 and PDL1 expression. Furthermore, adoptive transfer of B-1 cells lacking TCF1 and LEF1 fails to suppress brain inflammation. These transcription factors are also expressed in human chronic lymphocytic leukaemia B cells and in a B-1-like population that is abundant in pleural fluid and circulation of some patients with pleural infection. Our findings define a TCF1\u2013LEF1-driven transcriptional program that integrates stemness and regulatory function in B-1a cells.\n                  <\/jats:p>","DOI":"10.1038\/s41586-025-09421-0","type":"journal-article","created":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T15:04:20Z","timestamp":1755702260000},"page":"442-451","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["TCF1 and LEF1 promote B-1a cell homeostasis and regulatory function"],"prefix":"10.1038","volume":"646","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1899-6937","authenticated-orcid":false,"given":"Qian","family":"Shen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan 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