Defective mitochondria remodelling in B cells leads to an aged immune response

Marta Iborra-Pernichi, Jonathan Ruiz García, María Velasco de la Esperanza, Belén S. Estrada, Elena R. Bovolenta, Claudia Cifuentes, Cristina Prieto Carro, Tamara González Martínez, José García-Consuegra, María Fernanda Rey-Stolle, Francisco Javier Rupérez, Milagros Guerra Rodriguez, Rafael J. Argüello, Sara Cogliati, Fernando Martín-Belmonte and Nuria Martínez-Martín ()
Additional contact information
Marta Iborra-Pernichi: Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid
Jonathan Ruiz García: Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid
María Velasco de la Esperanza: Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid
Belén S. Estrada: Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid
Elena R. Bovolenta: Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid
Claudia Cifuentes: Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid
Cristina Prieto Carro: Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid
Tamara González Martínez: Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid
José García-Consuegra: Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid
María Fernanda Rey-Stolle: CEU Universities
Francisco Javier Rupérez: CEU Universities
Milagros Guerra Rodriguez: ” Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid
Rafael J. Argüello: Centre d’Immunologie de Marseille-Luminy
Sara Cogliati: Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid
Fernando Martín-Belmonte: Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid
Nuria Martínez-Martín: Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid

Nature Communications, 2024, vol. 15, issue 1, 1-20

Abstract: Abstract 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.

Date: 2024
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DOI: 10.1038/s41467-024-46763-1

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