Dynamic Mitochondrial Transcription and Translation in B Cells Control Germinal Center Entry and Lymphomagenesis

Overview

Journal Nat Immunol

Date 2023 Apr 24

PMID 37095377

Authors

Yavuz F Yazicioglu

Eros Marin

Ciaran Sandhu

Silvia Galiani

Iwan G A Raza

Mohammad Ali

Barbara Kronsteiner

Ewoud B Compeer

Moustafa Attar

Susanna J Dunachie

Michael L Dustin

Alexander J Clarke

Affiliations

Soon will be listed here.

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.

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