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

• Main Authors: Sergio Cepeda, Carolina Cantu, Stephanie Orozco, Yangming Xiao, Zoe Brown, Manpreet K. Semwal, Thomas Venables, Mark S. Anderson, Ann V. Griffith
• Format: Article
• Language: English
• Published: Elsevier 2018-01-01
• Series: Cell Reports
• Online Access: http://www.sciencedirect.com/science/article/pii/S2211124718300329

Summary: 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. : Mechanisms governing age-associated increases in autoimmunity remain elusive. Expression of Aire and downstream self-antigens by thymic B cells helps tolerize developing T cells. Cepeda et al. report age-associated declines in expression of Aire and self-antigen genes in thymic B cells concomitant with increases in T-bet and IgG2a expression. Keywords: thymus, B cell, aging, Aire