| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1995: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1994: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1993: ¥800,000 (Direct Cost: ¥800,000)
|
|---|
| 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.
|
