Mitochondrial dysfunction in B cells: a driver of an aged immune response
Nuria Martínez-Martín
Centro De Biología Molecular Severo Ochoa
The Germinal Centre (GC) reaction demands a unique bioenergetic supply. Despite B-cell mitochondria remodelling upon antigen encounter is crucial for sustaining these demands, mitochondria function in B cells is still poorly understood. To address this point, we have generated mice whose B cells lack Tfam, a transcription factor for mitochondria biogenesis.
Tfam KO mice displayed a blockage of GC reaction, establishing an immune response featured by the differentiation of activated B cells towards memory B cells and aged related B cells, hallmarks of an aged immune response. Unexpectedly, GC blockage in Tfam KO mice did not cause defects in the bioenergetic supply. In contrast, the Tfam KO GC phenotype was provoked by a defect in remodelling the lysosome compartment of B cells, unmasking a new mitochondria's function critical for antigen presentation during the GC reaction.
Our findings unveil a new mitochondria´s function during the GC reaction, whose abrogation seeds the basis of an aged immune response.