title: B-cell anergy induces a Th17 shift in a novel B lymphocyte transgenic NOD mouse model, the 116C-NOD mouse.
abstract: 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 selection mechanisms (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.
authors.affiliation: Immunology Unit, Department of Experimental Medicine, Faculty of Medicine, University of Lleida and IRBLleida, Lleida, Spain.
authors.forename: Jorge
authors.initials: J
authors.lastname: Carrascal
authors.affiliation: Immunology Unit, Department of Experimental Medicine, Faculty of Medicine, University of Lleida and IRBLleida, Lleida, Spain.
authors.forename: Jorge
authors.initials: J
authors.lastname: Carrillo
authors.affiliation: Immunology Unit, Department of Experimental Medicine, Faculty of Medicine, University of Lleida and IRBLleida, Lleida, Spain.
authors.forename: Berta
authors.initials: B
authors.lastname: Arpa
authors.affiliation: Immunology Unit, Department of Experimental Medicine, Faculty of Medicine, University of Lleida and IRBLleida, Lleida, Spain.
authors.forename: Leire
authors.initials: L
authors.lastname: Egia-Mendikute
authors.affiliation: Immunology Unit, Department of Experimental Medicine, Faculty of Medicine, University of Lleida and IRBLleida, Lleida, Spain.
authors.forename: Estela
authors.initials: E
authors.lastname: Rosell-Mases
authors.affiliation: Immunology Department, Institut d'Investigacio Germans Trias i Pujol, Badalona, Barcelona, Spain.
authors.forename: Irma
authors.initials: I
authors.lastname: Pujol-Autonell
authors.affiliation: Immunology Department, Institut d'Investigacio Germans Trias i Pujol, Badalona, Barcelona, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: Planas
authors.affiliation: Immunology Unit, Department of Experimental Medicine, Faculty of Medicine, University of Lleida and IRBLleida, Lleida, Spain.
authors.forename: Conchi
authors.initials: C
authors.lastname: Mora
authors.affiliation: Department of Endocrinology, Hospital Germans Trias i Pujol, Badalona, Barcelona, Spain.|CIBER of Diabetes and Associated Metabolic Diseases (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Dídac
authors.initials: D
authors.lastname: Mauricio
authors.affiliation: Immunology Department, Institut d'Investigacio Germans Trias i Pujol, Badalona, Barcelona, Spain.
authors.forename: Rosa Maria
authors.initials: RM
authors.lastname: Ampudia
authors.affiliation: Immunology Department, Institut d'Investigacio Germans Trias i Pujol, Badalona, Barcelona, Spain.|CIBER of Diabetes and Associated Metabolic Diseases (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Vives-Pi
authors.affiliation: Immunology Unit, Department of Experimental Medicine, Faculty of Medicine, University of Lleida and IRBLleida, Lleida, Spain.|CIBER of Diabetes and Associated Metabolic Diseases (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Joan
authors.initials: J
authors.lastname: Verdaguer
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D017635:Clonal Anergy; D017637:Clonal Deletion; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D004195:Disease Models, Animal; D007108:Immune Tolerance / Q000235:genetics* / Q000276:immunology; D008213:Lymphocyte Activation; D016688:Mice, Inbred NOD; D008822:Mice, Transgenic; D010641:Phenotype; D013154:Spleen / Q000033:anatomy & histology / Q000166:cytology / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology*; D019076:Transgenes
chemical_list: D016207:Cytokines
keywords: B lymphocyte; Immune tolerance; NOD mouse; Th17; Transgenic; Type 1 diabetes