FIGURE 2. Progressive differentiation and plasticity models of Tfh13 cell induction.

One possible pathway for Tfh13 cell induction is that Tfh13 cells progressively differentiate from IL-21⁺ Tfh cells (A, B). IL-21⁺ Tfh cells are induced early during an immune response, and they differentiate into IL-4-producing Tfh2 cells by up-regulating BATF, which induces IL-4 but not IL-5 or IL-13 production. These Tfh2 cells could in turn differentiate into Tfh13 cells through GATA3 upregulation (A). Alternatively, Tfh13 cells may also arise directly from IL-21⁺ Tfh cells (B). In contrast to progressive differentiation, a plasticity model suggests that Tfh13 cells and Tfh2 cells differentiate from Th2 cells (C). This pathway may be bi-directional as Tfh cells could also acquire a Th2 phenotype and migrate to the periphery as effector cells