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Study on B cell subsets producing ongan-specific autoantibodies

产生翁根特异性自身抗体的B细胞亚群的研究

基本信息

批准号：
02670281
负责人：
IWATANI Yoshinori
金额：
$ 0.38万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1990
资助国家：
日本
起止时间：
1990 至 1991
项目状态：
已结题

项目摘要

CD5^+B cells and CD5^-B cells are present in a B cell subpopulation. We previously found that CD5^+B cells are increased in autoimmune thyroid disease as well as in other autoimmune diseases. The number of CD5^+B cells is increased more in the hyperthyroid state than in the euthyroid state in Graves' disease, and is correlated with the serum levels of thyroid hormones or thyroid autoantibodies. Therefore, we examined which subset of B cells produces thyroid autoantibodies, and whether thyroid hormones may increase CD5^+B cells.We separated CD5^+B cells and CD5^-B cells from peripheral blood mononuclear cells from patients with autoimmune thyroid disease by using a cell sorter (FACStar). Each subset of B cells was cultured for 7 days with feeder cells of irradiated autologous lymphocytes in stimulation with B and T cell mitogens. Then, we clarified that CD5-B cells produce IgG-class of thyroid-peroxidase antibodies and of thyroglobulin antibodies by using ELISPOT assay. However, we did not identify a B cell subset producing TSH-receptor antibodies. Interestingly, IgM-class of thyroid autoantibodies was produced by both CD5^+B and CD5^-B cells.On the other hand, we administrated thyroxine or PTU to C57BL/6J mice for 1-6 months to make hyper- or hypothyroid mice. Splenic lymphocyte subsets were examined by two-clour flow cytomotry. NK cells and T cells were increased in hyperthyroid mice, and CD5^-B cells were increased in hypothyroid mice. CD5^+B cells were did not change with the serum levels of thyroid hormone. Furthermore, CD5^+B cells decreased in patients with destructive thyrotoxicosis due to the aggravation of Hashimoto's disease, even though the serum levels of thyroid hormones increased.These data suggest that CD5^+B cells may affect the production of thyroid-antibodies by CD5^-B cells, and that the increase of CD5^+B cells might be fundamental in the pathogenosis of Graves' disease.

CD 5 ^+B细胞和CD 5 ^-B细胞存在于B细胞亚群中。我们以前发现，CD 5 ^+B细胞在自身免疫性甲状腺疾病以及其他自身免疫性疾病中增加。Graves病甲亢患者的CD 5 ^+B细胞数比正常患者增加更多，并与血清甲状腺激素或甲状腺自身抗体水平相关。因此，我们研究了哪种B细胞亚群产生甲状腺自身抗体，以及甲状腺激素是否可以增加CD 5 ^+B细胞。我们使用细胞分选仪（FACStar）从自身免疫性甲状腺疾病患者的外周血单个核细胞中分离了CD 5 ^+B细胞和CD 5 ^-B细胞。将每个B细胞亚群与用B和T细胞有丝分裂原刺激的经辐射的自体淋巴细胞的饲养细胞一起培养7天。然后，我们阐明了CD 5-B细胞产生IgG类甲状腺过氧化物酶抗体和甲状腺球蛋白抗体，通过使用ELISPOT测定。然而，我们没有发现一个B细胞亚群产生TSH受体抗体。有趣的是，IgM类甲状腺自身抗体是由CD 5 ^+B和CD 5 ^-B细胞产生的。用双色流式细胞仪检测脾淋巴细胞亚群。甲状腺功能亢进小鼠NK细胞和T细胞增加，甲状腺功能减退小鼠CD 5 ^-B细胞增加。CD 5 ^+B细胞不随血清甲状腺激素水平变化。此外，在桥本病病情加重的破坏性甲状腺毒症患者中，尽管血清甲状腺激素水平升高，但CD 5 ^^+B细胞减少，提示CD 5 ^+B细胞可能影响CD 5 ^-B细胞产生甲状腺抗体，CD 5 ^+B细胞的增加可能是Graves病发病的基础。