An IL21 reporter mouse reveals a novel population of TFH precursors in young mice. (LYM8P.630)

Abstract

Abstract T follicular helper cells (TFH) are a specific subset of activated CD4+ T cells that localize to germinal centers (GC) and secrete Interleukin 21 (IL21). IL21 is vital for driving the proliferation of antigen-stimulated B cells within GC and their differentiation into memory B cells and antibody-secreting plasma cells. TFH and IL21 are crucial for normal humoral immunity, but their dysregulation has been implicated in immunodeficiencies and autoimmune diseases. However, the processes that result in the normal development of TFH and their expression of IL21 are still poorly understood. Here we use a novel IL21-venus fluorescent protein (VFP) reporter mouse to investigate the signals and pathways involved in the early differentiation of TFH and expression of IL21. Using this approach, we have identified a naturally occurring population of IL21-expressing CD44hi CD4+ T cells that are detected in the thymus and periphery of naïve C57BL/6J mice by 2 wks of age. RNAseq profiling and adoptive transfer experiments showed that these IL21-expressing cells are the earliest identified precursor (termed nascent TFH, nTFH) to the fully mature TFH state. nTFH display a highly diverse TCR repertoire, but restricting their TCR to a high affinity foreign antigen does not prevent their development. From this, we propose that nTFH arise by tonic self-antigenic stimulation and are primed for efficient differentiation to mature TFH in response to foreign or autoimmune antigen challenges.