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

ABSTRACT: 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.

SUBMITTER: Xu S 

PROVIDER: S-EPMC12260582 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature