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- Title
Defective mitochondria remodelling in B cells leads to an aged immune response.
- Authors
Iborra-Pernichi, Marta; Ruiz García, Jonathan; Velasco de la Esperanza, María; Estrada, Belén S.; Bovolenta, Elena R.; Cifuentes, Claudia; Prieto Carro, Cristina; González Martínez, Tamara; García-Consuegra, José; Rey-Stolle, María Fernanda; Rupérez, Francisco Javier; Guerra Rodriguez, Milagros; Argüello, Rafael J.; Cogliati, Sara; Martín-Belmonte, Fernando; Martínez-Martín, Nuria
- 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. B cell activation in the germinal centre (GC) is accompanied by metabolic adaptation, but the functions of mitochondria remodelling during this process is unclear. Here the authors find that B cell-specific deficiency of Tfam, a transcription factor modulating mitochondria remodelling, impacts GC responses and induces aged immune features in B cells.
- Subjects
B cells; B cell differentiation; B cell receptors; IMMUNE response; IMMUNOLOGIC memory; MITOCHONDRIA; CELL physiology
- Publication
Nature Communications, 2024, Vol 15, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-024-46763-1