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

被引:31
作者
Carrillo, J
Puertas, MC
Alba, A
Ampudia, RM
Pastor, X
Planas, R
Riutort, N
Alonso, N
Pujol-Borrell, R
Santamaria, P
Vives-Pi, M
Verdaguer, J
机构
[1] Hosp Badalona Germans Trias & Pujol, Serv Immunol, LIRAD, Badalona 08916, Barcelona, Spain
[2] Hosp Badalona Germans Trias & Pujol, Ctr Transuf & Tissue Bank CTBT, Badalona 08916, Barcelona, Spain
[3] Univ Autonoma Barcelona, Dept Cell Biol Physiol & Immunol, E-08193 Barcelona, Spain
[4] Hosp Badalona Germans Trias & Pujol, Serv Endocrinol, Badalona 08916, Barcelona, Spain
[5] Univ Calgary, Dept Microbiol & Infect Dis, Calgary, AB, Canada
[6] Univ Calgary, Julia McFarlane Diabet Res Ctr, Calgary, AB, Canada
关键词
D O I
10.2337/diabetes.54.1.69
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 insulitic 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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页码:69 / 77
页数:9
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