title: Direct evidence for the contribution of B cells to the progression of insulitis and the development of diabetes in non-obese diabetic mice.
abstract: The non-obese diabetic (NOD) mouse is an excellent animal model of autoimmune diabetes associated with insulitis. The progression of insulitis causes the destruction of pancreatic beta cells, resulting in the development of hyperglycemia. Although it has been well documented that T cells are required for the development of insulitis and diabetes in NOD mice, the importance of B cells remains unclear. To clarify the role of B cells in the pathogenesis of NOD mice, we therefore generated B cell-deficient NOD (B-NOD) mice. Surprisingly, none (of 13) of the B-NOD mice developed diabetes by 40 weeks of age, while the control littermates with B cells (B+NOD) suffered from a high proportion (43 of 49) of diabetes. The insulin reactivity of B+NOD mice was significantly impaired, while the B-NOD mice showed a good insulin response, thus suggesting the pancreatic beta cell function to be well preserved in B-NOD mice. Although B-NOD mice did develop insulitis, the extent of insulitis was significantly suppressed. These data thus provide the direct evidence that B cells are essential for the progression of insulitis and the development of diabetes in NOD mice.
authors.affiliation: First Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Akashi
authors.forename: S
authors.initials: S
authors.lastname: Nagafuchi
authors.forename: K
authors.initials: K
authors.lastname: Anzai
authors.forename: S
authors.initials: S
authors.lastname: Kondo
authors.forename: D
authors.initials: D
authors.lastname: Kitamura
authors.forename: S
authors.initials: S
authors.lastname: Wakana
authors.forename: J
authors.initials: J
authors.lastname: Ono
authors.forename: M
authors.initials: M
authors.lastname: Kikuchi
authors.forename: Y
authors.initials: Y
authors.lastname: Niho
authors.forename: T
authors.initials: T
authors.lastname: Watanabe
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology*; D003921:Diabetes Mellitus, Experimental / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D004195:Disease Models, Animal; D005951:Glucose Tolerance Test; D007515:Islets of Langerhans; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD / Q000235:genetics / Q000276:immunology; D010182:Pancreatic Diseases / Q000276:immunology; D013997:Time Factors