ANALYSIS OF SUPPRESSION OF AUTOIMMUNE DIABETES IN B-CELL DEFICIENT NOD MICE.

1997 Fiscal Year Final Research Report Summary

• Project/Area Number: 08671170
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: 内分泌・代謝学
• Research Institution: KYUSHU UNIVERSITY
• Principal Investigator: NAGAFUCHI Seiho KYUSHU UNIVERSITY,FACULTY OF MEDICINE,ASSISTANT, 医学部, 助手 (00150441)
• Co-Investigator(Kenkyū-buntansha): OTSUKA Takeshi KYUSHU UNIVERSITY,FACULTY OF MEDICINE,ASSISTANT, 医学部, 助手 (50213773) ; WATANABE Takeshi KYUSHU UNIVERSITY,INSTITUTE OF MEDICAL BIOREGULATION,PROFESSOR, 生体防御医学研究所, 教授 (40028684) ; AKASHI Tomoyuki KYUSHU UNIVERSITY,FACULTY OF MEDICINE,SENIOR RESIDENT, 医学部, 医員
• Project Period (FY): 1996 – 1997
• Keywords: DIABETES / INSULITIS / BLYMPHOCYTES / NOD MOUSE / Bリンパ球 / NODマウス / lprマウス / ノックアウトマウス

Research 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 essentially 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 (0/13) of the B-NOD mice developed diabetes by 40 weeks of age, while the control littermates with B cells (B+NOD) suffered from diabetes in a high proportion (43/49). 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.

Research Products

• [Publications] Akashi K, Nagafuchi S, Anzai K, et al.: "Direct evidence for the contribution of B'cells to the progression of Insulitis and the development of diabetes in non-obese diabetic mice." International Immunology. 9. 2259-2264 (1997)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Akashi K, Nagafuchi S, Kitamura D, et al.: "Proliferation of CD3+B220-Single positive normal T Cells was Suppressed in B cell-deficient lpr mice." Immunology. (1998)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Anzai K, Nagafuchi S, Kikuchi M, et al.: "B2-glyloprotein 1 -dependent and -independent anti-cardiolipin antibody in NOD mice." Clin exp Immunol. 111. 173-180 (1998)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Akashi K,Nagafuchi S,Anzai K,Kondo s ; Kitamura D,Wakana S,Ono J,Kikuchi M,Niho Y,Watanabe T.: "Direct evidence for the contribution of B cells to the progression of insulitits and the development of diabetes in non-obese diabetic mice." Int Immuno. 9. 2259-2264 (1997)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Anzai K,Nagafuchi S,Kikuchi M.Niho Y,Ono J.: "beta2-Glycoprotein 1 -dependent and-inde-pendent anticardiolipin antibody in NOD mice." Clin exp Immunol. 111. 173-180 (1998)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Akashi T,Nagafuchi S,Kitamura D,Anzai K,Wang J,Taniuchi I,Niho Y,Watanabe T.: "Proliferation of CD3+B220-single positive normal T cells was suppressed in B cell-deficient lpr mice." Immunology. (in press.).
  • Description: 「研究成果報告書概要(欧文)」より