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- Title
Prediabetes Induced by a Single Autoimmune B Cell Clone.
- Authors
Phillips, Nathaniel; Ke, Eugene; Nham, Amy; Seidl, Maximilian; Freeman, Brent; Abadejos, Justin R.; Xiao, Changchun; Nemazee, David; Ku, Manching; Kirak, Oktay
- Abstract
While B cells play a significant role in the onset of type-1 diabetes (T1D), little is know about their role in those early stages. Thus, to gain new insights into the role of B cells in T1D, we converted a physiological early pancreas-infiltrating B cell into a novel BCR mouse model using Somatic Cell Nuclear Transfer (SCNT). Strikingly, SCNT-derived B1411 model displayed neither developmental block nor anergy. Instead, B1411 underwent spontaneous germinal center reactions. Without T cell help, B1411-Rag1−/− was capable of forming peri-/intra-pancreatic lymph nodes, and undergoing class-switching. RNA-Seq analysis identified 93 differentially expressed genes in B1411 compared to WT B cells, including Irf7, Usp18 , and Mda5 that had been linked to a potential viral etiology of T1D. We also found various members of the oligoadenylate synthase (OAS) family to be enriched in B1411, such as Oas1 , which had recently also been linked to T1D. Strikingly, when challenged with glucose B1411-Rag1−/− mice displayed impaired glucose tolerance.
- Subjects
B cells; SOMATIC cell nuclear transfer; CLONE cells; PREDIABETIC state; T cells
- Publication
Frontiers in Immunology, 2020, Vol 11, p1
- ISSN
1664-3224
- Publication type
Article
- DOI
10.3389/fimmu.2020.01073