Journal article
Dynamic mitochondrial transcription and translation in B cells control germinal center entry and lymphomagenesis
- Abstract:
- Germinal center (GC) B cells undergo proliferation at very high rates in a hypoxic microenvironment but the cellular processes driving this are incompletely understood. Here we show that the mitochondria of GC B cells are highly dynamic, with significantly upregulated transcription and translation rates associated with the activity of transcription factor A, mitochondrial (TFAM). TFAM, while also necessary for normal B cell development, is required for entry of activated GC precursor B cells into the germinal center reaction; deletion of Tfam significantly impairs GC formation, function and output. Loss of TFAM in B cells compromises the actin cytoskeleton and impairs cellular motility of GC B cells in response to chemokine signaling, leading to their spatial disorganization. We show that B cell lymphoma substantially increases mitochondrial translation and that deletion of Tfam in B cells is protective against the development of lymphoma in a c-Myc transgenic mouse model. Finally, we show that pharmacological inhibition of mitochondrial transcription and translation inhibits growth of GC-derived human lymphoma cells and induces similar defects in the actin cytoskeleton.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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- Files:
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(Preview, Version of record, pdf, 7.7MB, Terms of use)
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- Publisher copy:
- 10.1038/s41590-023-01484-3
Authors
- Publisher:
- Springer Nature
- Journal:
- Nature Immunology More from this journal
- Volume:
- 24
- Issue:
- 6
- Pages:
- 991–1006
- Publication date:
- 2023-04-24
- Acceptance date:
- 2023-03-09
- DOI:
- EISSN:
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1529-2916
- ISSN:
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1529-2908
- Language:
-
English
- Keywords:
- Pubs id:
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1334132
- Local pid:
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pubs:1334132
- Deposit date:
-
2023-03-24
Terms of use
- Copyright holder:
- Yazicioglu et al
- Copyright date:
- 2023
- Rights statement:
- ©2023 The Author(s). This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
- Licence:
- CC Attribution (CC BY)
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