Role of class II molecule and T cell receptor in autoantibody production.

II 类分子和 T 细胞受体在自身抗体产生中的作用。

• 批准号: 63570169
• 负责人: HIROSE Sachiko
• 金额: $ 1.09万
• 依托单位: Juntendo 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: 1988
• 资助国家: 日本
• 起止时间: 1988 至 1989
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-63570169/
• 关键词: New Zealand mice; Systemic lupus erythematosus; Major histocompatibility complex; T cell receptor; Anti-DNA antibody; Congenic New Zealand mice; Class II molecule; ニュージーランドマウス; 全身性エリテマトーデス; 主要組織適合遺伝子複合体; コンジェニックマウス

As compared with the NZB strain, NZB x NZW F1 (B/W F1) hybrid mice show a much earlier onset and a higher incidence of renal disease, associated with markedly increased serum levels of anti-DNA antibodies. The increment of anti-DNA antibodies is mainly due to the increase in IgG class antibodies. These events in the B/W F1 mice can be attributed to the contribution of genes derived from both NZB and nonautoimmune NZW strains. Our studies using H-2 congenic New Zealand mice suggested that both H-2^d from NZB mice and H-2^z from NZW mice were required for IgG anti-DNA antibody production in B/W F1 mice. Our data also suggested that the gene linked to the T cell receptor beta chain gene complex of NZW has an important role in this event. The in vitro studies revealed that IgG anti-DNA antibody production in B/W F1 mice is strictly dependent on the interaction of antibody producing B cells and CD4^+ helper T cells. Together with these genetical and cellular studies, it is strongly suggested that the interplay between the hybrid Ia molecules derived from both NZB and NZW on B cells and T cell receptor from NZW may be essential for the production of IgG anti-DNA antibodies in B/W F1 mice.The requirement of H-2 heterozygosity for IgG anti-DNA antibody production was confirmed by the studies using H-2 congenic New Zealand mice, which we have already established. We are now trying to establish T cell receptor beta chain congenic New Zealand mice and to confirm the important role of T cell receptor for IgG anti-DNA antibody production in both in vivo and in vitro systems.

与NZ B系小鼠相比，NZ B x NZW F1（B/W F1）杂交小鼠肾脏病发病早，发病率高，血清抗DNA抗体水平明显升高。抗DNA抗体的增加主要是由于IgG类抗体的增加。B/W F1小鼠中的这些事件可归因于源自NZB和非自身免疫性NZW品系的基因的贡献。我们使用H-2同源新西兰小鼠的研究表明，来自NZ B小鼠的H-2 ^d和来自NZW小鼠的H-2 ^z都是B/W F1小鼠产生IgG抗DNA抗体所必需的。我们的数据还表明，与NZW的T细胞受体β链基因复合物相连的基因在这一事件中起重要作用。体外研究表明，B/W F1小鼠中IgG抗DNA抗体的产生严格依赖于产生抗体的B细胞和CD 4 ^+辅助T细胞的相互作用。结合这些遗传学和细胞学研究，强烈提示来源于NZB和NZW的杂合Ia分子在B细胞和来自NZW的T细胞受体上的相互作用可能是B/WF 1小鼠中产生IgG抗DNA抗体所必需的。这是我们已经建立的。我们现在正试图建立T细胞受体β链同源新西兰小鼠，并在体内和体外系统中证实T细胞受体对IgG抗DNA抗体产生的重要作用。

项目成果

Hasegawa,K.,Abe,M.,Okada,T.,Hirose,S.et al.: "Are Lyl B cells responsible for the IL-2 hyperresponsiveness of B cells in autoimmune-prone NZB × NZW F1 mice?" Int.Immunol.1. 99-101 (1989)

Hasekawa, K.、Abe, M.、Okada, T.、Hirose, S. 等人：“Lyl B 细胞是否导致自身免疫倾向 NZB × NZW F1 小鼠中 B 细胞的 IL-2 高反应性？” .免疫学.1。99-101 (1989)

広瀬幸子: 感染・炎症・免疫. 18. 81-88 (1988)

广濑幸子：感染、炎症和免疫。18. 81-88 (1988)。

広瀬幸子: "マウス内在性レトロウィルスと自己免疫疾患ーその遺伝的統御ー" 感染,炎症,免疫. 18. 81-88 (1988)

Sachiko Hirose：“小鼠内源性逆转录病毒和自身免疫性疾病 - 它们的遗传控制”《感染、炎症、免疫学》18. 81-88 (1988)。

Ohgaki,M.;Ueda,G.;Shiota,J.;Nishimura,H.;Hirose,S.;et al.: Submitted for publication.

Ohgaki,M.；Ueda,G.；Shiota,J.；Nishimura,H.；Hirose,S.；等人：已提交出版。

Okada,T.,Abe,M.,Takiura,F.,Hirose,S.et al.: "Distinct cell surface phenotypes of B cells spontaneously producing IgM and IgG anti-DNA antibodies in autoimmune-prone NZB × NZW F1 mice." Autoimmunity.

Okada, T.、Abe, M.、Takiura, F.、Hirose, S. 等人：“在易发生自身免疫的 NZB × NZW F1 小鼠中，B 细胞自发产生 IgM 和 IgG 抗 DNA 抗体的独特细胞表面表型。 “自身免疫。