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

Autor: 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, Nuria Martínez-Martín
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Nature Communications, Vol 15, Iss 1, Pp 1-20 (2024)
Druh dokumentu: article
ISSN: 2041-1723
DOI: 10.1038/s41467-024-46763-1
Popis: 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.
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