HVCN1 modulates BCR signal strength via regulation of BCR-dependent generation of reactive oxygen species
Open accessAbstract
Voltage-gated proton currents regulate generation of reactive oxygen species (ROS) in phagocytic cells. In B cells, stimulation of the B cell antigen receptor (BCR) results in the production of ROS that participate in B cell activation, but the involvement of proton channels is unknown. We report here that the voltage-gated proton channel HVCN1 associated with the BCR complex and was internalized together with the BCR after activation. BCR-induced generation of ROS was lower in HVCN1-deficient B cells, which resulted in attenuated BCR signaling via impaired BCR-dependent oxidation of the tyrosine phosphatase SHP-1. This resulted in less activation of the kinases Syk and Akt, impaired mitochondrial respiration and glycolysis and diminished antibody responses in vivo. Our findings identify unanticipated functions for proton channels in B cells and demonstrate the importance of ROS in BCR signaling and downstream metabolism.
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B cell receptor (BCR) activation is regulated by ROS.
“Along with these changes in metabolism, B cell receptor (BCR) activation is regulated by ROS (Capasso et al., 2010; Singh et al., 2005).”
From Mitochondria in the Regulation of Innate and Adaptive Immunity (2015) · cites this paper as Capasso et al., 2010
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Mitochondria in the Regulation of Innate and Adaptive Immunity
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- Authors
- Capasso, M., Bhamrah, M. K., Henley, T., Boyd, R. S., Langlais, C., Cain, K., Dinsdale, D., Pulford, K., Khan, M., Musset, B., Cherny, V. V., Morgan, D., Gascoyne, R. D., Vigorito, E., DeCoursey, T. E., MacLennan, I. C. M., & Dyer, M. J. S.
- Affiliations
- University of Leicester (GB)
- Babraham Institute (GB)
- University of Birmingham (GB)
- Rush University Medical Center (US)
- BC Cancer Agency (CA)
- Corresponding author
- Dyer, Martin J S
- ORCID
- Venue
- Nature Immunology
- Published
- 2010-02-07
- Volume
- 11
- Issue
- 3
- Pages
- 265-272
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- PMC
- PMC3030552
- OpenAlex
- W2051249711
- Cited by
- 223
- References
- 53
- Citations by year
- 2026: 5 · 2025: 13 · 2024: 9 · 2023: 16 · 2022: 10 · 2021: 13 · 2020: 18 · 2019: 16 · 2018: 13 · 2017: 8 · 2016: 17 · 2015: 21 · 2014: 11 · 2013: 12 · 2012: 18
- FWCI
- 7.29
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Immunology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Leicester Research Archive (University of Leicester) (submittedVersion)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
- Funders
- National Heart, Lung, and Blood Institute (HL 61437, R01HL061437)
- National Institute of General Medical Sciences (R01GM087507)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Keywords
- HVCN1, voltage-gated proton channel, B cell receptor signaling, reactive oxygen species, Syk, Akt signaling, mitochondrial respiration, glycolysis, B cell activation, antibody response, receptor internalization
- MeSH terms
- Syk Kinase, Animals, B-Lymphocytes, Enzyme Activation, Ion Channels, Mitochondria, Protein-Tyrosine Kinases, Receptors, Antigen, B-Cell, Immunoblotting, Signal Transduction, Reactive Oxygen Species, Mice, Knockout, Microscopy, Confocal, Intracellular Signaling Peptides and Proteins, Oncogene Protein v-akt, Mice
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