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Updated: Apr 24, 2026
In Vitro Differentiation Model of Human Normal Memory B Cells to Long-lived Plasma Cells
Published on: January 20, 2019
Bcl-6 directly represses the gene program of the glycolysis pathway
Kenneth J Oestreich1, Kaitlin A Read2, Sarah E Gilbertson3
11] Department of Immunology, University of Washington, Seattle, Washington, USA. [2] Virginia Tech Carilion Research Institute, Roanoke, Virginia, USA. [3] Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Tech, Blacksburg, Virginia, USA.
Abstract:
Despite the increasing knowledge of the molecular events that induce the glycolysis pathway in effector T cells, very little is known about the transcriptional mechanisms that dampen the glycolysis program in quiescent cell populations such as memory T cells. Here we found that the transcription factor Bcl-6 directly repressed genes encoding molecules involved in the glycolysis pathway, including Slc2a1, Slc2a3, Pkm and Hk2, in type 1 helper T cells (TH1 cells) exposed to low concentrations of interleukin 2 (IL-2). Thus, Bcl-6 had a role opposing the IL-2-sensitive glycolytic transcriptional program that the transcription factors c-Myc and HIF-1α promote in effector T cells. Additionally, the TH1 lineage-specifying factor T-bet functionally antagonized the Bcl-6-dependent repression of genes encoding molecules in the glycolysis pathway, which links the molecular balance of these two factors to regulation of the metabolic gene program.
Insights
The transcription factor Bcl-6 suppresses glycolysis in memory T cells by repressing key glycolytic genes. T-bet counteracts this repression, balancing T cell metabolism.
Area of Science:
- Immunology
- Cell Metabolism
- Molecular Biology
Background:
- The transcriptional regulation of glycolysis in effector T cells is well-understood.
- Mechanisms dampening glycolysis in quiescent memory T cells remain largely unknown.
Purpose of the Study:
- To investigate the transcriptional mechanisms that regulate the glycolysis pathway in quiescent memory T cells.
- To identify key transcription factors involved in suppressing glycolysis in type 1 helper T (TH1) cells.
Main Methods:
- Analysis of gene expression in TH1 cells under varying conditions.
- Investigating the role of transcription factors Bcl-6, c-Myc, HIF-1α, and T-bet.
- Focus on genes encoding glycolytic pathway molecules such as Slc2a1, Slc2a3, Pkm, and Hk2.
Main Results:
- Bcl-6 was found to directly repress genes involved in glycolysis (Slc2a1, Slc2a3, Pkm, Hk2) in TH1 cells treated with low interleukin-2 (IL-2).
- Bcl-6 opposes the IL-2-sensitive glycolytic program promoted by c-Myc and HIF-1α in effector T cells.
- T-bet antagonized Bcl-6-mediated repression of glycolytic genes.
Conclusions:
- Bcl-6 plays a critical role in suppressing the glycolysis pathway in quiescent memory T cells.
- The balance between Bcl-6 and T-bet influences the metabolic gene program in TH1 cells.
- This study links transcription factor activity to metabolic regulation in T cell populations.
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