The transcription factor Bcl11a is essential for B-1a cell maintenance during aging

• 成果类型: Article
• 署名作者: Xu, Shasha; Huang, Liangfeng; Liu, Xingjie; Zhang, Linlin; Wang, Jing; Hu, Yifeng; Yang, Yi; Shi, Xiaojie; Liu, Chaohong; Wang, Rong; Miao, Zhichao; Yu, Yong
• 署名单位: Tongji University; Tongji University; Tongji University; Tongji University; Huazhong University of Science & Technology; Huazhong University of Science & Technology; Youjiang Medical University for Nationalities; Guangzhou Medical University; Guangzhou Laboratory
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-11237
• DOI: 10.1073/pnas.2501974122
• 发表日期: 2025-07-08
• 关键词: b-cells; mice; repertoire; responses; distinct; lineage; layer

摘要

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. Bcl11a deletion reduced B- 1a cell numbers, impaired viability, and increased apoptosis across sexes and ages. Mechanistically, Bcl11a sustains survival by upregulating antiapoptotic genes rescue of viability defects in Bcl11a- deficient B- 1a cells upon p53 deletion. Conversely, cell maintenance during aging and reveal its role in mitigating sex- dimorphic immune decline through transcriptional control of survival pathways.