Autophagy is dispensable for B-cell development but essential for humoral autoimmune responses

Cell Death Differ. 2016 May;23(5):853-64. doi: 10.1038/cdd.2015.149. Epub 2015 Nov 20.

Abstract

To gain new insight into the role of B-cell autophagy, we generated two novel mouse models deficient for the autophagy-related gene (Atg)5, one from the outset pro-B cell stage (Atg5(f/-) Mb1 cre) and the other in mature B cells only (Atg5(f/-) CD21 cre). We show that autophagy is dispensable for pro- to pre-B cell transition, but necessary at a basal level to maintain normal numbers of peripheral B cells. It appears non-essential for B-cell activation under B-cell receptor stimulation but required for their survival after lipopolysaccharide stimulation that drives plasmablast differentiation and for specific IgM production after immunization. Results obtained using Atg5(f/-) CD21 cre × C57BL/6(lpr/lpr) autoimmune-prone mice show that B-cell autophagy is involved in the maintenance of anti-nuclear antibody secretion, elevated number of long-lived plasma cells, and sustains IgG deposits in the kidneys. Thus, treatments specifically targeting autophagy might be beneficial in systemic autoimmune diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoimmunity / immunology*
  • Autophagy / immunology*
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / pathology*
  • Cells, Cultured
  • Mice
  • Mice, Inbred C57BL