Reducing or increasing β-cell apoptosis without inflammation does not affect diabetes initiation in neonatal NOD mice

The presentation of islet antigens in the pancreatic LNs (PLNs) of mice is a developmentally regulated process. It has been hypothesized that, during physiological tissue remodeling, a wave of neonatal beta-cell apoptosis may initiate diabetes in autoimmune-prone strains of mice. If true, increasing or decreasing physiological beta-cell apoptosis in neonatal NOD mice should alter the time-course of antigen presentation in the PLNs. We used transgenic over-expression of either an anti-apoptotic protein (Bcl-2) or a toxic transgene (rat insulin promoter-Kb) in mouse beta cells to reduce or increase neonatal beta-cell apoptosis, respectively. Neither intervention affected the timing of antigen presentation in the PLNs or the initiation of islet infiltration. This suggests that under physiological conditions and in the absence of inflammation, neonatal beta-cell apoptosis in NOD mice is not the trigger for antigen presentation in the draining LNs.