T follicular helper cells (Tfh) are essential for the formation of germinal center (GC) reactions, and positive selection of GC B cells. Interrogating their role in an ongoing GC reaction has been challenging as few in vivo models manipulate Tfh cells in established GCs. Here, we use an Il21 fate mapping (Il21-fm) mouse to genetically target Tfh cells enabling their deletion at the peak of the GC reaction. We show that although Tfh cells are required for driving ongoing GC B cell proliferation, an established GC can withstand their temporary absence. The regenerative capacity of Tfh cells results in rejuvenation of the GC and return of affinity maturation. This recovery suggests the GC has evolved to cope with environmental stresses such as co-infection-associated immune-suppression, ensuring the generation of enduring humoral immunity.
