Journal article
BCL6 orchestrates Tfh cell differentiation via multiple distinct mechanisms
The Journal of experimental medicine, v 212(4), pp 539-553
04 Apr 2015
PMID: 25824819
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Follicular helper T cells (Tfh cells) are required for T cell help to B cells, and BCL6 is the defining transcription factor of Tfh cells. However, the functions of BCL6 in Tfh cells have largely remained unclear. Here we defined the BCL6 cistrome in primary human germinal center Tfh cells to assess mechanisms of BCL6 regulation of CD4 T cells, comparing and contrasting BCL6 function in T and B cells. BCL6 primarily acts as a repressor in Tfh cells, and BCL6 binding was associated with control of Tfh cell migration and repression of alternative cell fates. Interestingly, although some BCL6-bound genes possessed BCL6 DNA-binding motifs, many BCL6-bound loci were instead characterized by the presence of DNA motifs for AP1 or STAT. AP1 complexes are key positive downstream mediators of TCR signaling and external stimuli. We show that BCL6 can directly bind AP1, and BCL6 depends on AP1 for recruitment to BCL6-binding sites with AP1 motifs, suggesting that BCL6 subverts AP1 activity. These findings reveal that BCL6 has broad and multifaceted effects on Tfh biology and provide insight into how this master regulator mediates distinct cell context-dependent phenotypes.
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Details
- Title
- BCL6 orchestrates Tfh cell differentiation via multiple distinct mechanisms
- Creators
- Katerina Hatzi - Cornell UniversityJ. Philip Nance - La Jolla Institute for ImmunologyMark A. Kroenke - La Jolla Institute for ImmunologyMarcella Bothwell - Rady Children's Hospital-San DiegoElias K. Haddad - Vaccine & Gene Therapy Institute of FloridaAri Melnick - Cornell UniversityShane Crotty - La Jolla Institute for Immunology
- Publication Details
- The Journal of experimental medicine, v 212(4), pp 539-553
- Publisher
- Rockefeller Univ Press
- Number of pages
- 15
- Grant note
- S10RR027366 / NATIONAL CENTER FOR RESEARCH RESOURCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Research Resources (NCRR) AI109976; R01 AI072543 / National Institutes of Health (NIH); United States Department of Health & Human Services; National Institutes of Health (NIH) - USA R01 AI106482 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA Chemotherapy Foundation U19AI109976; UM1AI100663; R01AI106482; R01AI072543 / NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID) Burroughs Wellcome Foundation; Burroughs Wellcome Fund March of Dimes R01 104348 / National Cancer Institute; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- College of Medicine; Infectious Diseases (and HIV Medicine); Drexel University
- Web of Science ID
- WOS:000352281000009
- Scopus ID
- 2-s2.0-84928253323
- Other Identifier
- 991020099053904721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Immunology
- Medicine, Research & Experimental