NF-κB2 is required for the control of autoimmunity by regulating the development of medullary thymic epithelial cells

Academic Article


  • Medullary thymic epithelial cells function as antigen-presenting cells in negative selection of self-reactive T cell clones, a process essential for the establishment of central self-tolerance. These cells mirror peripheral tissues through promiscuous expression of a diverse set of tissue-restricted self-antigens. The genes and signaling pathways that regulate the development of medullary thymic epithelial cells are not fully understood. Here we show that mice deficient in NF-κB2, a member of the NF-κB family, display a marked reduction in the number of mature medullary thymic epithelial cells that express CD80 and bind the lectin Ulex europaeus agglutinin-1, leading to a significant decrease in the extent of promiscuous gene expression in the thymus of NF-κB2-/- mice. Moreover, NF-κB2-/- mice manifest autoimmunity characterized by multiorgan infiltration of activated T cells and high levels of autoantibodies to multiple organs. A subpopulation of the mice also develops immune complex glomerulonephritis. These findings identify a physiological function of NF-κB2 in the development of medullary thymic epithelial cells and, thus, the control of self-tolerance induction. © 2006 by The American Society for Biochemistry and Molecular Biology, Inc.
  • Authors

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    Digital Object Identifier (doi)

    Author List

  • Zhang B; Wang Z; Ding J; Peterson P; Gunning WT; Ding HF
  • Start Page

  • 38617
  • End Page

  • 38624
  • Volume

  • 281
  • Issue

  • 50