PR001897 (Project)

Description:The germinal centre (GC) reaction requires a unique bioenergetic supply. Although mitochondria are remodelled upon antigen stimulation, mitochondrial function in B cells is still poorly understood. To gain a better understanding of the role of mitochondria in B cell function, we generated mice that lack, specifically in B cells, Tfam, a transcription factor necessary for mitochondrial biogenesis. Tfam knock-out (KO) mice displayed a blockage of the GC reaction and established 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, but this phenotype was associated with a defect in the remodelling of the lysosomal compartment in B cells. Therefore, these results may describe a new mitochondrial function for antigen presentation during the GC reaction, the abrogation of which may be the basis of an aged immune response.