Follicular Helper CD4 T Cells (TFH)

Abstract

T cell help to B cells is a fundamental aspect of adaptive immunity and the generation of immunological memory. Follicular helper CD4 T (TFH) cells are the specialized providers of B cell help. TFHcells depend on expression of the master regulator transcription factor Bcl6. Distinguishing features of TFHcells are the expression of CXCR5, PD-1, SAP (SH2D1A), IL-21, and ICOS, among other molecules, and the absence of Blimp-1 (prdm1). TFHcells are important for the formation of germinal centers. Once germinal centers are formed, TFHcells are needed to maintain them and to regulate germinal center B cell differentiation into plasma cells and memory B cells. This review covers TFHdifferentiation, TFHfunctions, and human TFHcells, discussing recent progress and areas of uncertainty or disagreement in the literature, and it debates the developmental relationship between TFHcells and other CD4 T cell subsets (Th1, Th2, Th17, iTreg).