Bcl-6 controlled TFH polarization and memory: the known unknowns

Upon antigenic activation in vivo, naïve CD4 T cells can differentiate into one of several helper (Th) subsets under the control of lineage-specifying transcription factors to tailor immune responses against different types of pathogens. Follicular T-helper (TFH) cells are a recently defined subset that is controlled by Bcl-6 and specializes in promoting B cell-mediated humoral immunity. TFH cells exhibit unique spatiotemporal and functional features, but it is not settled as to how Bcl-6 promotes the TFH development, how TFH cells relate to other Th subsets, and how TFH cells relate to memory. Here we review recent advances and crucial gaps in our understanding of Bcl-6-controlled TFH development and function.