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. 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).