Follicular helper T lymphocytes in health and disease

Figure 2 Regulation of Follicular helper T cell development. After antigen-presenting signaling of dendritic cells (DC) to CD4⁺ T cells during priming, achaete-scute homologue 2 (Ascl2) and B cell lymphoma 6 (Bcl-6) induced by the inducible costimulator (ICOS), trigger for T_FH differentiation program and inhibit Th1 and Th17 genes. Bcl-6 also controls germinal center (GC) B cell differentiation. B lymphocyte-induced maturation protein 1 (Blimp-1) and the T-box transcription factor (T-bet) regulate the function of Bcl-6 and favor the induction of a Th1 profile. Under low interleukin 2 (IL-2) conditions, excess of Bcl-6 counteracts Blimp-1 allowing expansion of the T_FH and reduction of the Th1 programs of differentiation. Initial priming is sufficient to acquire the T_FH markers but cognate B cells are needed for the subsequent maintenance stage. T_FH: Follicular helper T lymphocytes; CXCR5: Chemokine (C-X-C motif) receptor 5; Th: T helper.