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IP3R-mediated Ca2+ signaling controls B cell proliferation through metabolic reprogramming
Huayuan Tang1,2, Yali Li1,2, Shijia Wang1
1Department of Cardiovascular Surgery, Peking University Shenzhen Hospital, State Key Laboratory of Chemical Oncogenomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen, China.
Iscience
|May 2, 2022
Summary
Calcium signaling and calcineurin regulate B cell metabolism, proliferation, and survival by reprogramming cellular energy pathways. This impacts B cell receptor stimulation and may explain diseases linked to IP3R defects.
Area of Science:
- Immunology
- Cell Biology
- Metabolic Regulation
Background:
- Metabolic regulation is increasingly recognized as crucial for B cell activation and function.
- Calcium (Ca2+) signaling and calcineurin are key targets of immunosuppressants and may influence B cell metabolism.
Purpose of the Study:
- To investigate the role of IP3R-mediated Ca2+ signaling and calcineurin in regulating B cell metabolism, proliferation, and survival following B cell receptor (BCR) stimulation.
Main Methods:
- Utilized IP3R-triple-knockout (IP3R-TKO) B cells and calcineurin inhibition.
- Assessed metabolic reprogramming, including glucose uptake, oxidative phosphorylation, glycolysis, and mitochondrial remodeling.
- Investigated the calcineurin-MEF2C-Myc pathway.
Main Results:
- IP3R-TKO and calcineurin inhibition significantly suppressed metabolic reprogramming in stimulated B cells.
- Impaired metabolic switch led to reduced glucose uptake, altered glycolytic enzyme expression, and mitochondrial changes.
- This resulted in diminished cell-cycle entry and survival.
Conclusions:
- IP3R-mediated Ca2+ signaling and calcineurin are critical regulators of B cell metabolic adaptation and function.
- These pathways control B cell proliferation and survival by reprogramming metabolism post-BCR stimulation.
- Findings offer insights into inborn errors of immunity associated with IP3R defects.
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