title: Islet-infiltrating B-cells in nonobese diabetic mice predominantly target nervous system elements.
abstract: B-cells accumulate in pancreatic islets during the autoimmune response that precedes the onset of type 1 diabetes. However, the role and antigenic specificity of these cells remain a mystery. To elucidate the antigenic repertoire of islet-infiltrating B-cells in type 1 diabetes, we generated hybridoma cell lines of islet-infiltrating B-cells from nonobese diabetic (NOD) mice and NOD mice expressing a diabetogenic T-cell receptor (8.3-NOD). Surprisingly, characterization of the tissue specificity of the antibodies secreted by these cells revealed that a predominant fraction of these hybridomas produce antibodies specific for the pancreatic nervous system. Similar results were obtained with B-cell hybridomas derived from mild insulinic lesions of diabetes-resistant (NOD x NOR)F1 and 8.3-(NOD x NOR)F1 mice. Immunoglobulin class analyses further indicated that most islet-derived hybridomas had arisen from B-cells that had undergone immunoglobulin class switch recombination, suggesting that islet-associated B-cells are involved in active, T-helper-driven immune responses against local antigenic targets. This is the first evidence showing the existence of a predominant active B-cell response in situ against pancreatic nervous system elements in diabetogenesis. Our data are consistent with the idea that this B-cell response precedes the progression of insulitis to overt diabetes, thus strongly supporting the idea that pancreatic nervous system elements are early targets in type 1 diabetes.
authors.affiliation: Servei d'Immunologia, Hospital Universitari Germans Trias i Pujol, Carretera del Canyet s/n, 08916 Badalona, Barcelona, Spain.
authors.forename: Jorge
authors.initials: J
authors.lastname: Carrillo
authors.forename: Maria Carmen
authors.initials: MC
authors.lastname: Puertas
authors.forename: Aurora
authors.initials: A
authors.lastname: Alba
authors.forename: Rosa Maria
authors.initials: RM
authors.lastname: Ampudia
authors.forename: Xavier
authors.initials: X
authors.lastname: Pastor
authors.forename: Raquel
authors.initials: R
authors.lastname: Planas
authors.forename: Nadal
authors.initials: N
authors.lastname: Riutort
authors.forename: Nuria
authors.initials: N
authors.lastname: Alonso
authors.forename: Ricardo
authors.initials: R
authors.lastname: Pujol-Borrell
authors.forename: Pere
authors.initials: P
authors.lastname: Santamaria
authors.forename: Marta
authors.initials: M
authors.lastname: Vives-Pi
authors.forename: Joan
authors.initials: J
authors.lastname: Verdaguer
mesh_terms: D000818:Animals; D003433:Crosses, Genetic; D003922:Diabetes Mellitus, Type 1 / Q000145:classification / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D005260:Female; D006825:Hybridomas; D007136:Immunoglobulins / Q000235:genetics; D007515:Islets of Langerhans / Q000473:pathology*; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D009420:Nervous System / Q000473:pathology*
chemical_list: D007136:Immunoglobulins