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

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 mitochon...

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Detalles Bibliográficos
Autores: Iborra Pernichi, Marta, Ruiz García, Jonathan, Velasco de la Esperanza, María, Estrada, Belén S., Bovolenta, Elena R., Cifuentes, Claudia, Prieto Castro, Cristina, González Martínez, Tamara, García-Consuegra Martínez, José, Rey Stolle, María Fernanda, Rupérez, Francisco Javier, Guerra Rodriguez, Milagros, Argüello, Rafael J., Cogliati, Sara, Martín Belmonte, Fernando, Martínez Martín, Nuria
Tipo de recurso: artículo
Fecha de publicación:2024
País:España
Institución:Universidad Autónoma de Madrid
Repositorio:Biblos-e Archivo. Repositorio Institucional de la UAM
Idioma:inglés
OAI Identifier:oai:repositorio.uam.es:10486/717069
Acceso en línea:http://hdl.handle.net/10486/717069
https://dx.doi.org/10.1038/s41467-024-46763-1
Access Level:acceso abierto
Palabra clave:Animals
b-lymphocytes
germinal center
lymphocyte activation
mice
knockout
mitochondria
Biología y Biomedicina / Biología
Descripción
Sumario: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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