A novel population of interleukin 21-producing pre-follicular T helper cells develop spontaneously in young naïve mice (LYM3P.743)

Abstract

Abstract Interleukin 21 is a cytokine vital for driving the proliferation of antigen-stimulated B cells within the germinal center and their subsequent differentiation into antibody-secreting plasmablasts and plasma cells. IL21 is predominately produced by a subset of activated CD4+ T cells known as T follicular helper cells. These cells develop at the T cell-B cell border and express ICOS, PD1, CD44, CXCR5 and BCL6. While this cell type has been identified, the processes that ultimately result in TFH differentiation are poorly understood. Here we use a novel IL21-venus fluorescent protein reporter mouse to investigate the signals and pathways involved in the earliest stages of development of TFH cells and production of IL21. We identify and characterize a naturally occurring population of ICOShi CD44hi CD4+ T cells that produce IL21 and are present within 4 weeks of age in naïve healthy C57BL/6J mice. These T cells show characteristics of TFH cells, including the upregulation of Bcl6 and Sostdc1, but lack surface staining for CXCR5 and PD1 and, surprisingly, develop in the absence of B cells. Therefore, these spontaneously arising cells actively producing IL21 appear to identify the earliest precursor to the mature TFH state.