Islet-infiltrating B-cells in nonobese diabetic mice predominantly target nervous system elements.
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.
Carrillo
Jorge
J
Servei d'Immunologia, Hospital Universitari Germans Trias i Pujol, Carretera del Canyet s/n, 08916 Badalona, Barcelona, Spain.
Puertas
Maria Carmen
MC
Alba
Aurora
A
Ampudia
Rosa Maria
RM
Pastor
Xavier
X
Planas
Raquel
R
Riutort
Nadal
N
Alonso
Nuria
N
Pujol-Borrell
Ricardo
R
Santamaria
Pere
P
Vives-Pi
Marta
M
Verdaguer
Joan
J
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*
D007136:Immunoglobulins