Abnormalities in B cell subsets and immunoglobulins in patients with premature ovarian insufficiency

Immune disturbance has long been considered as a component of premature ovarian insufficiency (POI), but the distribution of B cell subsets and immunoglobulins (Igs) remains largely unclear. 75 patients with POI, 83 with biochemical POI (bPOI) and 155 control women were recruited, and the number, phenotype and function of peripheral B subsets, levels of total Igs and IgG subclasses in serum and follicular fluid (FF) were examined. Compared to control women, POI patients showed significantly increased numbers of total B cells, with increased proportions of naive B and decreased class-switched memory B, plasma cells, and CD19+IL-10+ B regulatory cells (Bregs). The decrease in Bregs was mainly contributed by decline in CD19+CD24hiCD27+ and CD19+CD24hiCD38hi Breg subsets, while the suppressive effect of CD19+CD24hiCD27+ Bregs on IFN-γ and TNF-α production of T cells were largely unaffected. Additionally, patients with POI or bPOI had decreased levels of IgG and IgM in either serum or FF, while the distribution of IgG subclasses in FF was comparable between groups. As ovarian follicles mature, increased level of IgG and decreased IgM in FF were observed. Of note, the quantity of total B, naïve B subsets, Bregs and Igs were positively correlated with AMH, AFC and negatively with FSH in POI patients. Aberrant B subsets and decreased Igs in association with ovarian reserve decline were found in periphery and ovary of POI patients, contributing to the inflammatory microenvironment and ovarian dysfunction in POI. Our data provide new insights into autoimmune pathogenesis and clues for therapeutic interventions for POI.