Prediabetes Induced by a Single Autoimmune B cell Clone [ATAC-seq]

SCNT-derived B cell model displays spontaneous germinal center reaction, infiltration of pancreas (in RAG1-/- background) and impaired glucose tolerance. To better understand the role of B cells in autoimmune diabetes, we used somatic cell nuclear transfer (SCNT) to develop a novel model from a physiological pancreas-infiltrating B cell on pure non-obese diabetic (NOD) background. Contrary to previous transgenic autoimmune B cell models, the SCNT-derived B cell model (referred to as B1411) displayed neither a developmental block nor anergy. Instead, B1411 underwent spontaneous germinal center reaction, and on RAG1-deficient background B1411 was capable of infiltrating the pancreas, and of undergoing class-switch recombination. RNA-Seq analysis identified 93 differentially expressed genes in B1411, among which were Irf7, Usp18, Mda5 that had been linked to a potential viral etiology of autoimmune diabetes, as well as various members of the oligoadenylate synthase (OAS) family. Strikingly, when challenged with glucose B1411-Rag1-/- mice displayed impaired glucose tolerance.