T follicular cells: The regulators of germinal center homeostasis

The formation of high-affinity antibodies that protect against infection requires the formation of germinal centres (GCs), where specialized T follicular helper cells (Tfh) provide help to B cells. Those T-B interactions are critical in supporting isotype switching and affinity maturation of B cells. However, GC responses need to be tightly regulated by specialized Foxp3-expressing T follicular regulatory cells (Tfr). It has been shown that the failure of Tfr cells to regulate GC responses can lead to antibody-mediated autoimmunity. Hence, the balance between protection against infection versus tolerance towards self requires an appropriate regulation of cellular and molecular events within secondary lymphoid tissue. Here, we review the development and biology of these T follicular cell subsets, with special emphasis on the metabolic regulation of Tfh cells, thus contributing to a greater understanding of GC responses.