Expression and Role of the RNA‐Binding Protein, ZFP36L1, in Mouse T Follicular Helper Cell Differentiation and Function

ABSTRACT

T follicular helper (Tfh) cells are critical for germinal centers (GC), the specialized microenvironment where long‐lived humoral immunity is generated in response to vaccination or infection. Within the GC, B cells engage with Tfh cells and elicit their help in the form of cytokines and cell‐surface co‐stimulator molecules. Tfh helper activity must be rapidly available in response to B cell engagement, yet the mechanisms controlling this helper activity remain poorly characterized. Post‐transcriptional regulation of mRNA decay and translation offers one way to rapidly and temporally tune Tfh cell activity. ZFP36L1, a member of the ZFP family of RNA‐binding proteins, is a candidate modulator of Tfh cell helper activity, as it controls cytokine production and responses in other T cell lineages, modulating their differentiation and function. We sought to determine if ZFP36L1 is also important for Tfh cell biology. In this study, we show expression of ZFP36L1 by Tfh cells. We selectively delete ZFP36L1 from Tfh cells and analyze the effect this has on the GCs. Surprisingly, we find that the GC response and affinity maturation are resilient to deletion of ZFP36L1 from Tfh cells.