Peripheral B cell alteration in patients with premature ovarian insufficiency

Premature ovarian insufficiency (POI) is one of the most common diseases contributing to declining fertility globally. Autoimmune dysregulation has been implicated in POI, but the role of B cell and its subsets in immune dysregulation in POI remains unclear. In the current study, we investigated whether disturbances in the distribution and functional characteristics of peripheral B cell subsets are associated with POI and its severity. Our results revealed that POI patients exhibited a higher percentage of total CD19⁺ B cells, but the proportion of memory B cells (MBCs) and plasmablasts was significantly reduced compared to controls. A notable decrease in interleukin-10 (IL-10) production by B cells was observed, primarily due to a reduction in CD19⁺CD24^hiCD27⁺ and CD19⁺CD24^hiCD38^hi regulatory B cells (B_regs). These alterations correlated with elevated follicle-stimulating hormone (FSH) and decreased anti-Müllerian hormone (AMH) and antral follicle count (AFC) levels. However, no significant differences were observed in the suppressive capacity of B_regs on interferon-gamma (IFN-γ) or tumor necrosis factor-alpha (TNF-α) production by autologous CD4⁺ T cells in POI patients compared with control women. These findings suggest that B-cell dysregulation may contribute to the immune pathogenesis of POI, providing potential targets for therapeutic intervention.