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J Exp Med. 2016 May 30;213(6):967-78. doi: 10.1084/jem.20151869. Epub 2016 May 2.

Class-switched anti-insulin antibodies originate from unconventional antigen presentation in multiple lymphoid sites.

Author information

1
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110.
2
Department of Medicine, Vanderbilt University Medical School, Nashville, TN 37232.
3
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110 unanue@wustl.edu.

Abstract

Autoantibodies to insulin are a harbinger of autoimmunity in type 1 diabetes in humans and in non-obese diabetic mice. To understand the genesis of these autoantibodies, we investigated the interactions of insulin-specific T and B lymphocytes using T cell and B cell receptor transgenic mice. We found spontaneous anti-insulin germinal center (GC) formation throughout lymphoid tissues with GC B cells binding insulin. Moreover, because of the nature of the insulin epitope recognized by the T cells, it was evident that GC B cells presented a broader repertoire of insulin epitopes. Such broader recognition was reproduced by activating naive B cells ex vivo with a combination of CD40 ligand and interleukin 4. Thus, insulin immunoreactivity extends beyond the pancreatic lymph node-islets of Langerhans axis and indicates that circulating insulin, despite its very low levels, can have an influence on diabetogenesis.

PMID:
27139492
PMCID:
PMC4886365
DOI:
10.1084/jem.20151869
[Indexed for MEDLINE]
Free PMC Article

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