In vivo regulation of Bcl6 and T follicular helper cell development
| Autor: | Danelle Eto, Kyle Hansen, Joe Craft, Anmol Chandele, Xuemei Dong, Sairy Hernandez, Alexander L. Dent, Shane Crotty, Amanda C. Poholek, Susan M. Kaech, Jason S. Weinstein, Jared M. Odegard |
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| Rok vydání: | 2010 |
| Předmět: |
Cell signaling
Cellular differentiation medicine.medical_treatment Immunology Lymphocyte Cooperation Down-Regulation Mice Transgenic Cell Communication Biology Article Immunophenotyping Mice Downregulation and upregulation T-Lymphocyte Subsets hemic and lymphatic diseases Cricetinae medicine Immunology and Allergy Animals Mice Knockout Mice Inbred BALB C T follicular helper cell differentiation Membrane Glycoproteins Cell growth Germinal center Cell Differentiation T-Lymphocytes Helper-Inducer BCL6 Molecular biology Cell biology Up-Regulation DNA-Binding Proteins Mice Inbred C57BL Cytokine Proto-Oncogene Proteins c-bcl-6 Female Spleen |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 185(1) |
| ISSN: | 1550-6606 |
| Popis: | Follicular helper T (TFH) 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 TFH cell development. We found that TFH 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 TFH 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 TFH cell phenotype, including CXCR5 and PD-1 upregulation, and IL-21 synthesis. Bcl6 upregulation and TFH cell differentiation were independent of IL-6 and IL-21, revealing that either cytokine is not absolutely required for development of Bcl6+ TFH cells in vivo. These data increase our understanding of Bcl6 regulation in TFH cells and their differentiation in vivo and identifies a new surface marker that may be functionally relevant in this subset. |
| Databáze: | OpenAIRE |
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