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.Mahidol University2023-05-192023-05-192023-01-01Nature Immunology (2023)15292908https://repository.li.mahidol.ac.th/handle/123456789/81520Germinal 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.Immunology and MicrobiologyArticleSCOPUS10.1038/s41590-023-01484-32-s2.0-8515333460515292916