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. 2005 Jan;54(1):69-77.
doi: 10.2337/diabetes.54.1.69.

Islet-infiltrating B-cells in nonobese diabetic mice predominantly target nervous system elements

Jorge Carrillo  1 , Maria Carmen Puertas, Aurora Alba, Rosa Maria Ampudia, Xavier Pastor, Raquel Planas, Nadal Riutort, Nuria Alonso, Ricardo Pujol-Borrell, Pere Santamaria, Marta Vives-Pi, Joan Verdaguer
Affiliations

Islet-infiltrating B-cells in nonobese diabetic mice predominantly target nervous system elements

Jorge Carrillo et al. Diabetes. 2005 Jan.

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.

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