Age-Associated Decline in Thymic B Cell Expression of Aire and Aire-Dependent Self-Antigens

Cell Rep. 2018 Jan 30;22(5):1276-1287. doi: 10.1016/j.celrep.2018.01.015.


Although autoimmune disorders are a significant source of morbidity and mortality in older individuals, the mechanisms governing age-associated increases in susceptibility remain incompletely understood. Central T cell tolerance is mediated through presentation of self-antigens by cells constituting the thymic microenvironment, including epithelial cells, dendritic cells, and B cells. Medullary thymic epithelial cells (mTECs) and B cells express distinct cohorts of self-antigens, including tissue-restricted self-antigens (TRAs), such that developing T cells are tolerized to antigens from peripheral tissues. We find that expression of the TRA transcriptional regulator Aire, as well as Aire-dependent genes, declines with age in thymic B cells in mice and humans and that cell-intrinsic and cell-extrinsic mechanisms contribute to the diminished capacity of peripheral B cells to express Aire within the thymus. Our findings indicate that aging may diminish the ability of thymic B cells to tolerize T cells, revealing a potential mechanistic link between aging and autoimmunity.

Keywords: Aire; B cell; aging; thymus.

Publication types

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

MeSH terms

  • AIRE Protein
  • Adult
  • Aging / immunology*
  • Aging / pathology
  • Animals
  • Autoantigens / biosynthesis*
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • Central Tolerance / immunology*
  • Child, Preschool
  • Humans
  • Infant
  • Mice
  • Middle Aged
  • Thymus Gland / immunology*
  • Thymus Gland / metabolism
  • Transcription Factors / biosynthesis*


  • Autoantigens
  • Transcription Factors