Progressively Differentiated Tfh13 Cells are Stabilized by JunB to Mediate Allergen Germinal Center Responses

Allergic diseases are common and affect a large proportion of the population. IL-13-expressing follicular T (Tfh13) cells are a newly identified population of Tfh cells that have been associated with high affinity IgE responses. However, the origins, developmental signals, transcriptional programming and precise functions of Tfh13 cells are unknown. Here, we examined the developmental signals for Tfh13 cells and found a direct and progressive differentiation pathway marked by the production of IL-21. These two pathways differed in kinetics and extrinsic requirements. However, both pathways converged, forming transcriptionally similar Tfh13 cells that express the transcription factor JunB as a critical stabilizing factor. Using an intersectional genetics-based Tfh13-DTR model to perturb these cells, we found that Tfh13 cells were essential to drive broad germinal center responses and allergen-specific IgG and IgE. Moreover, we found that IL-21 is a broad positive regulator of allergen germinal center B cells and synergizes with IL-13 produced by Tfh13 cells to amplify allergic responses. Thus, Tfh13 cells orchestrate multiple features of allergic inflammation. Overall design: Various subsets of lymph node T follicular helper cells in duplicate