Estrogen influences class-switched memory B cell frequency only in humans with two X chromosomes.

ABSTRACT: Sex differences in immunity are well-documented, though mechanisms underpinning these differences remain ill-defined. Here, in a human-only ex vivo study, we demonstrate that postpubertal cisgender females have higher levels of CD19+CD27+IgD- class-switched memory B cells compared with age-matched cisgender males. This increase is only observed after puberty and before menopause, suggesting a strong influence for sex hormones. Accordingly, B cells express high levels of estrogen receptor 2 (ESR2), and class-switch-regulating genes are enriched for ESR2-binding sites. In a gender-diverse cohort, blockade of natal estrogen in transgender males (XX karyotype) reduced class-switched memory B cell frequency, while gender-affirming estradiol treatment in transgender females (XY karyotype) did no

SUBMITTER: Peckham H 

PROVIDER: S-EPMC11893172 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature