Targeting T follicular helper cells for lifelong health

T follicular helper (T_FH) 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. T_FH 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. T_FH 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 T_FH 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, T_FH cells have been implicated in cancer, diabetes and atherosclerosis. Given the multifaceted roles of T_FH cells in health and disease, and the changes to their biology during normal ageing, the development of targeted strategies to modulate T_FH cell activity is an attractive approach to promote health across the lifespan.