GSE176047
Gene expression of wild-type and Nix-/-Bnip3-/- memory B cells
Memory B cells are long-lived lymphocytes essential for humoral immunological memory. Autophagy is required for the long-term survival of memory B cells, however, the molecular mechanisms for the protection by autophagy have not been fully elucidated. Here we show that mitochondrial autophagy mediated by Nix and Bnip3 prevents necroptosis in memory B cells by maintaining mitochondrial homeostasis and normal lipid metabolism. In mice with B cell-specific deletion of Nix and Bnip3, memory B cells showed significant increases in viable mitochondria and de novo fatty acid synthesis, with accumulation of lipid droplets in the cytoplasm and accelerated cell death. Inhibiting the mitochondrial citrate transporter Slc25a1 or silencing the necroptosis gene Ripk3 rescued Nix–/–Bnip3–/– memory B cells in vivo. These data indicate that Nix- and Bnip3-dependent mitochondrial autophagy in memory B cells is important for restricting de novo fatty acid synthesis and preventing necroptosis.  Our results suggest a mechanism for autophagy in the maintenance of mitochondrial homeostasis for the protection of immunological memory. Overall design: RNA-seq of WT and Nix-/-Bnip3-/- memory B cells