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

Author:
  • Sabine Bieg
  • William T Simonson
  • Kristian Ellefsen
  • Åke Lernmark
Publishing year: 2000-01
Language: English
Pages: 47-54
Publication/Series: Pancreas
Volume: 20
Issue: 1
Document type: Journal article
Publisher: Lippincott Williams & Wilkins

Abstract english

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-κB/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.

Keywords

  • Antigen-presenting cell
  • Congenic
  • Dendritic cell
  • Diabetes
  • Pancreas
  • T cell

Other

Published
  • ISSN: 0885-3177
E-mail: ake [dot] lernmark [at] med [dot] lu [dot] se

Principal investigator

Diabetes and Celiac Unit

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+46 70 616 47 79

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Jan Waldenströms gata 35, Malmö

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Lund University Diabetes Centre, CRC, SUS Malmö, Jan Waldenströms gata 35, House 91:12. SE-214 28 Malmö. Telephone: +46 40 39 10 00