Estrogen Modulation of B Cell Immunity: Implications for HIV Control and Therapeutic Strategies

Biological sex profoundly impacts HIV acquisition, disease progression, and persistence. Beyond genetic differences, sex hormones such as estrogen play multifaceted roles in shaping immune responses to HIV. However, the precise effects of estrogen and other sex hormones on the various components of the immune system, and their implications for HIV progression and persistence, remain poorly understood. Addressing these gaps is essential for developing strategies to improve the management of chronic HIV, especially in post-menopausal cisgender women and transgender women. B cells are crucial for HIV control, primarily through the production of anti-HIV antibodies. Emerging evidence suggests that estrogen exerts significant, yet underappreciated, effects on B cell function. However, the interactions between estrogen and B cells during HIV remain poorly characterized. This review explores current insights into the estrogen-B cell axis, emphasizing its role in modulating immune responses critical to HIV. Specifically, it examines estrogen's effects on B cell activation, antibody production, and antibody functionality, all of which can influence HIV control and disease progression. We also highlight key research gaps, including the impact of differential estrogen levels on immune-mediated HIV control and the potential of estrogen modulators to enhance B cell-driven immunity during HIV.