Increased NF‐κB activity in B cells and bone marrow‐derived dendritic cells from NOD mice

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 theimmune 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‐κB nuclear translocation is increased in unmanipulated NOD and NOD.B10Sn‐H2b B cells and that, inaddition, NOD B cells are more sensitive to NF‐κB‐activating stimuli. We obtained similar results using NOD bone marrow‐derived dendritic cell (BMDC) cultures. As costimulatory molecules havebeen shown to be NF‐κB 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‐κB 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.