Autoreactive B lymphocytes play a key role as APCs in diaebetogenesis. However, it remains unclear whether B-cell tolerance is compromised in NOD mice. Here, we describe a new B lymphocyte transgenic NOD mouse model, the 116C-NOD mouse, where the transgenes derive from an islet-infiltrating B lymphocyte of a (8.3-NODxNOR) F1 mouse. The 116C-NOD mouse produces clonal B lymphocytes with pancreatic islet beta cell specificity. The incidence of T1D in 116C-NOD mice is decreased in both genders when compared with NOD mice.Moreover, several immune selectionmechanisms (including clonal deletion and anergy) acting on the development, phenotype, and function of autoreactive B lymphocytes during T1D development have been identified in the 116C-NOD mouse. Surprisingly, a more accurate analysis revealed that, despite their anergic phenotype, 116C B cells express some costimulatory molecules after activation, and induce a T-cell shift toward a Th17 phenotype. Furthermore, this shift on T lymphocytes seems to occur not only when both T and B cells contact, but also when helper T (Th) lineage is established. The 116C-NOD mouse model could be useful to elucidate the mechanisms involved in the generation of Th-cell lineages. ; This work was supported by grants (SAF2006-06970 and SAF2009-09215) from the Plan Nacional de I+D+i of the Spanish Ministry of Science and Innovation, from CIBER of Diabetes and Associated Metabolic Diseases (CIBERDEM), which is an initiative from Instituto de Salud Carlos III (Spain), and from the Juvenile Diabetes Research Foundation 5- 2005-1133 innovative research grant. J.C. was supported by a FPI predoctoral fellowship (BES-2007-15221) from Spanish Ministry of Science and Innovation. I.P-A. and E.R. are FI predoctoral fellowships (2011FI B 01056 and 2013FIB00585, respectively) supported by the European Social Fund and the Secretary for Universities and Research, Department of Economics and knowledge of Catalan Government (Generalitat de Catalunya). M.V-P. and R.A. are researcher and research technician, respectively, supported by the Department of Health of Catalan Government. J.V. and C.M. are associate professors from the Serra-Hunter Program from the Catalan Government. We also thank Dr. T. Stratmann for reading the manuscript and Mrs. D. Cullell-Young for editorial assistance.