title: Rel B is an early marker of autoimmune islet inflammation in the biobreeding (BB) rat.
abstract: 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.
authors.affiliation: Robert H. Williams Laboratory, Department of Medicine, University of Washington, Seattle, USA. bieg@mail.uni-mainz.de
authors.forename: S
authors.initials: S
authors.lastname: Bieg
authors.forename: W
authors.initials: W
authors.lastname: Simonson
authors.forename: K
authors.initials: K
authors.lastname: Ellefsen
authors.forename: A
authors.initials: A
authors.lastname: Lernmark
mesh_terms: D000367:Age Factors; D000818:Animals; D020296:Animals, Congenic; D017951:Antigen Presentation; D001327:Autoimmune Diseases / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015415:Biomarkers; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation; D005838:Genotype; D007091:Image Processing, Computer-Assisted; D017403:In Situ Hybridization; D018664:Interleukin-12 / Q000096:biosynthesis / Q000235:genetics; D007515:Islets of Langerhans / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism; D010179:Pancreas / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D010195:Pancreatitis / Q000235:genetics* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D011236:Prediabetic State / Q000235:genetics* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000235:genetics; D051381:Rats; D011913:Rats, Inbred BB; D013950:Thymus Gland / Q000378:metabolism / Q000473:pathology; D051841:Transcription Factor RelB; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D015415:Biomarkers; D016328:NF-kappa B; D011518:Proto-Oncogene Proteins; C497595:Relb protein, rat; D014157:Transcription Factors; D051841:Transcription Factor RelB; D018664:Interleukin-12