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The Yin and Yang of Follicular Helper T Cells

The balanced expression of two transcription factors controls the development of a subset of T cells that support B cell maturation. The human immune system can harness an arsenal of lymphocytes called CD4+ T cells, in an adaptive response to infection by a variety of pathogens, including parasites, bacteria, and fungi. Once activated, CD4+ T cells can differentiate into subsets of helper T cells [TH1, TH2, TH17, regulatory T (Treg), and follicular T (TFH)], whose effector functions include secreting the cytokines necessary for clearing pathogens and inducing inflammatory responses. Each helper T cell subtype is also critical for helping B lymphocytes produce pathogen-specific antibodies (1). Until now, master transcription factors have been identified that regulate the generation of helper T cell lineages except for TFH cells. On pages 1006 and 1001 of this issue, Johnston et al. (2) and Nurieva et al. (3), and a study by Yu et al. (4), report that the transcription factor Bcl6 is a master transcription factor that controls the generation of TFH cells. However, Bcl6 must work against another transcription factor, Blimp-1, to promote this differentiation process.