T follicular helper cells in primary immune regulatory disorders.

CD4 T follicular helper (Tfh) cells are central to the formation of germinal centers and subsequent production of high-affinity antibodies through their interactions with B cells within lymphoid tissue. Although Tfh cells are important for robust serologic immunity against pathogens, self-reactive Tfh cells promotes autoantibody production, thereby disrupting immune tolerance. This review synthesizes studies that have elucidated the development and function of Tfh cells, mechanisms by which they cause autoimmunity, and the role of circulating Tfh cells as accessible biomarkers of disease activity. We use examples from primary immune regulatory disorders and common autoimmune disorders to illustrate the clinical impact of Tfh and circulating Tfh cell dysregulation. Finally, we discuss the therapeutic potential of targeting Tfh cells in autoimmune diseases.