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

Xiaoxiao Wan, James W. Thomas, Emil R. Unanue

Research output: Contribution to journalArticle

19 Scopus citations

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.

Original languageEnglish
Pages (from-to)967-978
Number of pages12
JournalJournal of Experimental Medicine
Volume213
Issue number6
DOIs
StatePublished - May 30 2016

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