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

Wan X, Thomas JW, Unanue ER
J Exp Med. 2016 213 (6): 967-78

PMID: 27139492 · PMCID: PMC4886365 · DOI:10.1084/jem.20151869

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.

© 2016 Wan et al.

MeSH Terms (13)

Animals Antigen Presentation B-Lymphocytes CD40 Antigens Diabetes Mellitus, Type 1 Germinal Center Immunoglobulin Class Switching Insulin Interleukin-4 Islets of Langerhans Mice Mice, Knockout T-Lymphocytes

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