Functional analysis of infiltrating lymphocytes in islets of NODmice by using gene targeting.

1995 Fiscal Year Final Research Report Summary

• Project/Area Number: 05670869
• Research Category: Grant-in-Aid for General Scientific Research (C)
• Allocation Type: Single-year Grants
• 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): KITAMURA Daisuki Tokyo Science University, Institute of Life Science, Professor, 生命科学研究所, 教授 (70204914)
• Project Period (FY): 1993 – 1995
• Keywords: Diabetes / insulitis / B lymphocytes / autoimmunity / NOD mouse

Research Abstract

Although the importance of lymphocytes in the development of insulitis and diabetes has been emphasized in NOD mice, the significance of B lymphocytes has not been determined. We has already reported that infiltrations of lymphocytes to islets(insulitis)consistrd not only of T lymphocytes but also B lymphoctyes, suggesting the pathogenic role of B lymohocytes in insulitis of NOD mice. In order to investigate the role of B lymphocytes in the development of insulitis and diabetes, we have made B lymphoctes deficient NOD mice. B lymphocytes deficent C57BL/6 mice was produced by disrupting the membrane exon of immunoglobulin mu chain by gene targeting(muMT). The muMT/+B57BL/6mice were backcrossed 8 time to NOD mice, and thus NOD mice carring muMT gene was established. The B cell deficiency was recognized as the absence of immunoglobulin positive lymphocytes in the preipheral blood of muMT/muMT NOD mice. To detemine the glucose intolerance, we measured blood sugar every 3 weeks until 35 weeks.
B lymphocyte deficient femal NOD mice (muMT/muMTn=17)and controls, whose genetic types were muMT/+or+/+(n=50), were analyzed.84%(42/50)of control mice(+/+, muMT/+)developed diabetes, while none(0/17)of B lymphocyte deficient muMT/muMT NOD mice induced diabetes, indicating that B lymphocytes were essential for the development of diabetes in NOD mice. The development of insulitis in B lymphocyte deficient NOD mice were observed as well as in control NOD mice, however, the degree of insulitis in B lymphocyte deficient muMT/muMT NOD mice was significantly less than that in control mice.
These results indicate that B lymphocytes are citically important for the development of insulitis and diabetes in NOD mice.