Increased NF-kappa B activity in B cells and bone marrow-derived dendritic cells from NOD mice

Eur J Immunol. 2004 May;34(5):1395-404. doi: 10.1002/eji.200324490.

Abstract

Type 1 diabetes results from the breakdown of peripheral tolerance. As regulators of T cell activation, antigen-presenting cells (APC) modulate peripheral tolerance and hence contribute to the immune dysregulation characteristic of insulin-dependent diabetes mellitus (IDDM). We initially observed an increased importance of NOD B cell APC function in a T cell priming assay as compared to non-autoimmune strains. Consistent with this increased APC function, we found that NF-kappa B nuclear translocation is increased in unmanipulated NOD and NOD.B10Sn-H2(b) B cells and that, in addition, NOD B cells are more sensitive to NF-kappa B-activating stimuli. We obtained similar results using NOD bone marrow-derived dendritic cell (BMDC) cultures. As costimulatory molecules have been shown to be NF-kappa B responsive, we examined the expression of these markers on NOD APC. Both B cells and BMDC expressed elevated levels of CD80 and CD40. Finally, NOD B cells provided better allostimulation than B cells from non-autoimmune strains. Therefore, hyperactivation of NF-kappa B and increased expression of CD80 and CD40 by NOD B cells and BMDC may be a contributing factor in the selection of effector T cells observed in IDDM.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigen-Presenting Cells / immunology
  • Autoantigens / immunology
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism*
  • Bone Marrow Cells / metabolism
  • Cell Nucleus / metabolism
  • Dendritic Cells / metabolism*
  • Insulin / immunology
  • Membrane Proteins / immunology
  • Mice
  • Mice, Inbred NOD
  • NF-kappa B / metabolism*
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1
  • Protein Tyrosine Phosphatases / immunology
  • Receptor-Like Protein Tyrosine Phosphatases, Class 8
  • T-Lymphocytes / immunology

Substances

  • Autoantigens
  • Insulin
  • Membrane Proteins
  • NF-kappa B
  • PTPRN2 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1
  • Protein Tyrosine Phosphatases
  • Receptor-Like Protein Tyrosine Phosphatases, Class 8