Protection of Quiescence and Longevity of IgG Memory B Cells by Mitochondrial Autophagy

J Immunol. 2022 Mar 1;208(5):1085-1098. doi: 10.4049/jimmunol.2100969. Epub 2022 Jan 31.


The development of long-lived immune memory cells against pathogens is critical for the success of vaccines to establish protection against future infections. However, the mechanisms governing the long-term survival of immune memory cells remain to be elucidated. In this article, we show that the maintenance mitochondrial homeostasis by autophagy is critical for restricting metabolic functions to protect IgG memory B cell survival. Knockout of mitochondrial autophagy genes, Nix and Bnip3, leads to mitochondrial accumulation and increases in oxidative phosphorylation and fatty acid synthesis, resulting in the loss of IgG+ memory B cells in mice. Inhibiting fatty acid synthesis or silencing necroptosis gene Ripk3 rescued Nix-/-Bnip3-/- IgG memory B cells, indicating that mitochondrial autophagy is important for limiting metabolic functions to prevent cell death. Our results suggest a critical role for mitochondrial autophagy in the maintenance of immunological memory by protecting the metabolic quiescence and longevity of memory B cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • Fatty Acids / biosynthesis
  • Homeostasis / physiology
  • Immunoglobulin G / immunology*
  • Immunologic Memory / immunology*
  • Longevity / immunology
  • Membrane Proteins / genetics
  • Memory B Cells / cytology
  • Memory B Cells / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mitochondria / metabolism*
  • Mitochondrial Proteins / genetics
  • Mitophagy / physiology*
  • Necroptosis / genetics
  • Oxidative Phosphorylation
  • RNA Interference
  • RNA, Small Interfering / genetics
  • Receptor-Interacting Protein Serine-Threonine Kinases / genetics


  • BNip3 protein, mouse
  • Fatty Acids
  • Immunoglobulin G
  • Membrane Proteins
  • Mitochondrial Proteins
  • Nix protein, mouse
  • RNA, Small Interfering
  • Receptor-Interacting Protein Serine-Threonine Kinases
  • Ripk3 protein, mouse