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 insulitis. Pancreas sections from prediabetic Lyp/Lyp, Lyp/+ and +/+ rats were analyzed by immunohistochemistry. We found W3/25+ cells in the exo- and endocrine 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 frequent in the parafollicular cortex of pancreatic lymph nodes from Lyp/Lyp than from Lyp/+ and +/+ rats. In the Lyp/Lyp thymus, we found significantly increased expression of IL-12p40 messenger RNA (mRNA; p<0.001), located in the Rel B-protein-rich corticomedullary junction. The NF-KB/Rel B complex specifically transactivates genes involved in antigen presentation in dendritic cells. Rel B+ cells in the islets may therefore mark the onset of autoimmune insulitis and antigen-specific activation of autoreactive T cells in the lymph nodes of diabetes prone Lyp/Lyp BB rats. In the thymus, Rel B+ cells may support the Lyp-dependent development of self-reactive thymocytes by activation of cytokine expression.