Targeting T follicular helper cells for lifelong health.

T follicular helper (TFH) cells support B cell function by promoting memory B cell differentiation and sustaining long-lasting antibody responses, thereby enabling immunity that protects the host from subsequent infections. TFH cells are essential for orchestrating the antibody-mediated immunity achieved via vaccination, which has had a profound global impact in reducing the morbidity and mortality associated with infectious diseases. TFH cells provide help to B cells both within and outside germinal centres and deliver key signals that drive immunoglobulin class switching and affinity maturation. The formation and function of TFH cells is dynamic and adaptable, with significant cellular plasticity to ensure that robust antibody production accompanies most immune responses. However, when antibodies are directed against self or non-pathogenic antigens, they can contribute to the development of autoimmune diseases, allergic reactions and transplant rejection. Beyond supporting antibody responses, TFH cells have been implicated in cancer, diabetes and atherosclerosis. Given the multifaceted roles of TFH cells in health and disease, and the changes to their biology during normal ageing, the development of targeted strategies to modulate TFH cell activity is an attractive approach to promote health across the lifespan.