The study investigates the role of Bcl6, a transcription factor selectively expressed in T follicular helper (TFH) cells, in the development of TFH cells and their function. Bcl6 expression is regulated by interleukin-6 (IL-6) and interleukin-21 (IL-21), and its overexpression induces TFH-related gene expression while inhibiting the differentiation of other TH lineage cells. Bcl6 deficiency in T cells results in impaired TFH cell development, reduced germinal center reactions, and altered production of other effector T cell subsets. The data suggest that Bcl6 is essential for the programming of TFH cell generation, acting as a master transcriptional factor in TFH cell differentiation.The study investigates the role of Bcl6, a transcription factor selectively expressed in T follicular helper (TFH) cells, in the development of TFH cells and their function. Bcl6 expression is regulated by interleukin-6 (IL-6) and interleukin-21 (IL-21), and its overexpression induces TFH-related gene expression while inhibiting the differentiation of other TH lineage cells. Bcl6 deficiency in T cells results in impaired TFH cell development, reduced germinal center reactions, and altered production of other effector T cell subsets. The data suggest that Bcl6 is essential for the programming of TFH cell generation, acting as a master transcriptional factor in TFH cell differentiation.