The development and fate of follicular helper T cells defined by an IL-21 reporter mouse

Germinal centers require CD4+ follicular helper T cells (T FH cells), whose hallmark is expression of the transcriptional repressor Bcl-6, the chemokine receptor CXCR5 and interleukin 21 (IL-21). To track the development and fate of TFH cells, we generated an IL-21 reporter mouse by introducing sequence encoding green fluorescent protein (GFP) into the Il21 locus; these mice had expression of IL-21-GFP in CD4 +CXCR5+PD-1+ TFH cells. IL-21-GFP+ TFH cells were multifunctional helper cells that coexpressed several cytokines, including interferon-? (IFN-?), IL-2 and IL-4. TFH cells proliferated and gave rise to transferrable memory cells with plasticity, which differentiated after recall into conventional effector helper T cells and TFH cells. Thus, we demonstrated that TFH cells were not terminally differentiated but instead retained the flexibility to be recruited into other helper T cell subsets and nonlymphoid tissues