Understanding the effect of estrogen on B cells: implications for immune health and autoimmunity

Estrogen is a steroid hormone involved in the regulation of multiple systems in the body. Among these, the immune system is of particular interest due to the significant female predominance seen in many autoimmune diseases. Since B cells and B-cell-driven antibody responses are central to the development of autoimmune diseases, the influence of estrogen on B cells has been extensively investigated. Throughout B-cell development, estrogen exerts complex and contrasting effects depending on the level of exposure to estrogen and the stage of development of the B cell. For instance, at early stages, high concentrations of estrogen negatively regulate early B-cell precursor development, whereas low baseline concentrations are stimulatory and essential. Conversely, estrogen exposure at later stages leads to increased rescue of autoreactive B cells, enabling their maturation and subsequent autoantibody production, a mechanism that contributes to the development of a systemic lupus erythematosus-like phenotype in murine models. Beyond rescuing autoreactive cells, estrogen can also modulate the function of germinal centers, where autoreactive antibodies may arise through somatic hypermutation. The complex interplay of these effects sets the stage for both the heightened immune response and increased autoimmunity observed in females. In this review, we will explore the various effects of estrogen on B cells to provide a comprehensive overview of the role of estrogen in shaping immune function and enhancing autoimmunity.