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- W4366824245 abstract "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." @default.
- W4366824245 created "2023-04-25" @default.
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- W4366824245 date "2023-04-24" @default.
- W4366824245 modified "2023-10-13" @default.
- W4366824245 title "Dynamic mitochondrial transcription and translation in B cells control germinal center entry and lymphomagenesis" @default.
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- W4366824245 doi "https://doi.org/10.1038/s41590-023-01484-3" @default.
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