| First Author | Yazicioglu YF | Year | 2023 |
| Journal | Nat Immunol | Volume | 24 |
| Issue | 6 | Pages | 991-1006 |
| PubMed ID | 37095377 | Mgi Jnum | J:337624 |
| Mgi Id | MGI:7495989 | Doi | 10.1038/s41590-023-01484-3 |
| Citation | Yazicioglu YF, et al. (2023) Dynamic mitochondrial transcription and translation in B cells control germinal center entry and lymphomagenesis. Nat Immunol 24(6):991-1006 |
| abstractText | 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. |
