Rel B is an early marker of autoimmune islet inflammation in the BioBreeding (BB) rat

Because the development of insulitis and diabetes is predictable in Lyp/Lyp congenic BB rats, we have characterized early islet inflammation in these rats to determine the cell subsets involved in the onset of autoimmune insu litis. Pancreas sections from prediabetic Lyp/Lyp, Lyp/+ and +/+ rats were analyzed by immunohistochemistry. We found W3/25+ cells in the exo- and end ocrine tissue from all three genotypes, but intraislet insulitis was never found in Lyp/+ or +/+ rats. The onset of massive, intraislet B- and T-cell infiltration in Lyp/Lyp rats was preceded by Rel B+ cells in and around the islets, followed by ED1+ monocytes/macrophages. Rel B+ cells were more fre quent in the parafollicular cortex of pancreatic lymph nodes from Lyp/Lyp t han from Lyp/+ and +/+ rats. In the Lyp/Lyp thymus, we found significantly increased expression of IL-12p40 messenger RNA (mRNA; p < 0.001), located i n the Rel B-protein-rich corticomedullary junction. The NF-kappa B/Rel B co mplex specifically transactivates genes involved in antigen presentation in dendritic cells. Rel B+ cells in the islets may therefore mark the onset o f autoimmune insulitis and antigen-specific activation of autoreactive T ce lls in the lymph nodes of diabetes prone Lyp/Lyp BE rats. In the thymus, Re l B+ cells may support the Lyp-dependent development of self-reactive thymo cytes by activation of cytokine expression.