Dynamic mitochondrial transcription and translation in B cells control germinal center entry and lymphomagenesis
1
Issued Date
2023-01-01
Resource Type
ISSN
15292908
eISSN
15292916
Scopus ID
2-s2.0-85153334605
Journal Title
Nature Immunology
Rights Holder(s)
SCOPUS
Bibliographic Citation
Nature Immunology (2023)
Suggested Citation
Yazicioglu Y.F., Marin E., Sandhu C., Galiani S., Raza I.G.A., Ali M., Kronsteiner B., Compeer E.B., Attar M., Dunachie S.J., Dustin M.L., Clarke A.J. Dynamic mitochondrial transcription and translation in B cells control germinal center entry and lymphomagenesis. Nature Immunology (2023). doi:10.1038/s41590-023-01484-3 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/81520
Title
Dynamic mitochondrial transcription and translation in B cells control germinal center entry and lymphomagenesis
Other Contributor(s)
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.