Iborra-Pernichi, M., Ruiz García, J., Velasco de la Esperanza, M., Estrada, B. S., Bovolenta, E. R., Cifuentes, C., Prieto Carro, C., González Martínez, T... Martín-Belmonte, F., & Martínez-Martín. Defective mitochondria remodelling in B cells leads to an aged immune response
Nat Commun. 2024
"Mitochondrial dysfunction in B cells unveil lysosome control during humoral immune response". - Marta Iborra Pernichi
Summary:
The B cell response in the germinal centre (GC) reaction requires a unique bioenergetic supply. Although mitochondria are remodelled upon antigen-mediated B cell receptor stimulation, mitochondrial function in B cells is still poorly understood.
To gain a better understanding of the role of mitochondria in B cell function, here we generate mice with B cell-specific deficiency in Tfam, a transcription factor necessary for mitochondrial biogenesis. Tfam conditional knock-out (KO) mice display a blockage of the GC reaction and a bias of B cell differentiation towards memory B cells and aged-related B cells, hallmarks of an aged immune response.
Unexpectedly, blocked GC reaction in Tfam KO mice is not caused by defects in the bioenergetic supply but is associated with a defect in the remodelling of the lysosomal compartment in B cells. Our results may thus describe a mitochondrial function for lysosome regulation and the downstream antigen presentation in B cells during the GC reaction, the dysruption of which is manifested as an aged immune response.
Why do you highlight this publication?
This work set light into the field of immunometabolism in B cell function, positioning the mitochondria as a central hub for proper immune response. Beyond energy support, mitochondria in B cells are an essential link in the functionality of the lysosome, controlling fundamental processes of the humoral response such as antigen presentation to T cells. The disruption of the mitochondria-lysosome axis manifests as an aged immune response.
Publication commented by:
Dr. Marta Iborra Pernichi
