Poholek, Amanda C.Hansen, KyleHernandez, Sairy G.Eto, DanelleChandele, AnmolWeinstein, Jason S.Dong, XuemeiOdegard, Jared M.Kaech, Susan M.Dent, Alexander L.Crotty, ShaneCraft, Joe2025-10-162025-10-162010Poholek AC, Hansen K, Hernandez SG, et al. In vivo regulation of Bcl6 and T follicular helper cell development. J Immunol. 2010;185(1):313-326. doi:10.4049/jimmunol.0904023https://hdl.handle.net/1805/51663Follicular helper T (T(FH)) cells, defined by expression of the surface markers CXCR5 and programmed death receptor-1 (PD-1) and synthesis of IL-21, require upregulation of the transcriptional repressor Bcl6 for their development and function in B cell maturation in germinal centers. We have explored the role of B cells and the cytokines IL-6 and IL-21 in the in vivo regulation of Bcl6 expression and T(FH) cell development. We found that T(FH) cells are characterized by a Bcl6-dependent downregulation of P-selectin glycoprotein ligand 1 (PSGL1, a CCL19- and CCL21-binding protein), indicating that, like CXCR5 and PD-1 upregulation, modulation of PSGL1 expression is part of the T(FH) cell program of differentiation. B cells were neither required for initial upregulation of Bcl6 nor PSGL1 downregulation, suggesting these events preceded T-B cell interactions, although they were required for full development of the T(FH) cell phenotype, including CXCR5 and PD-1 upregulation, and IL-21 synthesis. Bcl6 upregulation and T(FH) cell differentiation were independent of IL-6 and IL-21, revealing that either cytokine is not absolutely required for development of Bcl6(+) T(FH) cells in vivo. These data increase our understanding of Bcl6 regulation in T(FH) cells and their differentiation in vivo and identifies a new surface marker that may be functionally relevant in this subset.en-USPublisher PolicyImmunophenotypingDNA-binding proteinsMembrane glycoproteinsSpleenArticle