{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T08:30:08Z","timestamp":1789029008547,"version":"build-2803163510"},"reference-count":59,"publisher":"National Academy of Sciences","issue":"27","license":[{"start":{"date-parts":[[2025,7,3]],"date-time":"2025-07-03T00:00:00Z","timestamp":1751500800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"the Natural science foundation of china","doi-asserted-by":"crossref","award":["82371736"],"award-info":[{"award-number":["82371736"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100012166","name":"National key R&D program of China","doi-asserted-by":"crossref","award":["2021YFA1100903"],"award-info":[{"award-number":["2021YFA1100903"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2025,7,8]]},"abstract":"<jats:p>\n                    B-1a cells, a self-renewing B cell subset essential for innate immunity, produce natural IgM antibodies that defend against pathogens, yet mechanisms sustaining their maintenance during aging remain unclear. We report that aging B-1a cells exhibit hallmarks of decline, including DNA damage, apoptosis, and reduced proliferation, with striking sex-specific disparities: aged females retain higher B-1a cell numbers than males, correlating with enhanced glycolysis and chromatin accessibility. Motif analysis of accessible regions identified the transcription factor Bcl11a, which shows elevated chromatin accessibility and expression in aged female B-1a cells but declines in males.\n                    <jats:italic toggle=\"yes\">Bcl11a<\/jats:italic>\n                    deletion reduced B-1a cell numbers, impaired viability, and increased apoptosis across sexes and ages. Mechanistically, Bcl11a sustains survival by upregulating antiapoptotic genes (\n                    <jats:italic toggle=\"yes\">Mcl1<\/jats:italic>\n                    ,\n                    <jats:italic toggle=\"yes\">Mdm2<\/jats:italic>\n                    , and\n                    <jats:italic toggle=\"yes\">Mdm4<\/jats:italic>\n                    ) to suppress p53-mediated apoptosis, as evidenced by partial rescue of viability defects in Bcl11a-deficient B-1a cells upon\n                    <jats:italic toggle=\"yes\">p53<\/jats:italic>\n                    deletion. Conversely, Bcl11a overexpression or Bcl11a-high B-1a cells from aged\n                    <jats:italic toggle=\"yes\">Bcl11a<\/jats:italic>\n                    -eGFP reporter mice enhanced stress resistance. These findings establish Bcl11a as a key regulator of B-1a cell maintenance during aging and reveal its role in mitigating sex-dimorphic immune decline through transcriptional control of survival pathways.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2501974122","type":"journal-article","created":{"date-parts":[[2025,7,3]],"date-time":"2025-07-03T13:20:24Z","timestamp":1751548824000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":4,"title":["The transcription factor Bcl11a is essential for B-1a cell maintenance during aging"],"prefix":"10.1073","volume":"122","author":[{"given":"Shasha","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Hematology, Tongji Hospital, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University","place":["Shanghai, 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