Effect of depletion of Tfam on gene expression in stimulated B cells
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 a 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 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. Overall design: To investigate the impact of Tfam deletion in activated B cells, we sorted and stimulated in vitro B cells from WT and Tfamfl/fl Mb1Cre+ (KO) mice. RNA was purified and we performed gene expression profiling analysis using data obtained from RNAseq of 4 different mice for each genotype (WT and KO).