Analysis of the function of bone marrow stromal cell antigen, BST-1 (CD157) to support B cells

骨髓基质细胞抗原 BST-1 (CD157) 支持 B 细胞的功能分析

• 批准号: 10670301
• 负责人: ISHIHARA Katsuhiko
• 金额: $ 1.92万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670301/
• 关键词: CD157; stromal cell; B cell; Rheumatoid arthritis; knockout mouse; CD38; 抗体産生; ectoenzyme; ストロ-マ細胞

(1) Roles for BST-1 in arthritis induced by type 2 collagen : Soluble BST-1 transgenic mice (a line S15) and wild type mice (n=6 and 8, respectively), which had been backcrossed with DBA/1J for 8 generations, were immunized with 100μg of bovine type 2 collagen and incomplete Freund adjuvant. Although the incidence of arthritis in S15 mice increased from those of wild mice. The incidence of arthritis in BST-1KO mice, which had been backcrossed with DBA/1J (N=15) for 5generations ,was higher than that of wild mice (n=13) at day 57 (100% and 69%, respectively). There was no difference in the severity. BST-1 does not have important roles in collagen induced arthritis.(2) Generation of BST-1/CD38 double knockout mouse : ES cell clones deleted both CD38 and BST-1 genes were selected and the chimeric mice were obtained. Analysis of F1 generation revealed successful targeting of CD38 and BST-1 genes will be obtained by crossing the mice of F1 generation.(3) Receptor function :Crosslinking of BST-1 on the surface of mBST-1BAF, a pro B cell line transfected with murine BST-1 cDNA, resulted in the cell aggregation, indicating that signals through BST-1 induce cell adhesion.(4) BST-1Ligand: cDNA library for expression cloning was prepared form a B cell line which binds BST-1. Candidates of cDNA for human BST-1ligand has not been obtained after screening of 2x10ィイD14ィエD1 clones.

(1)BST-1在2型胶原诱导的关节炎中的作用：用100μg牛2型胶原和不完全弗氏佐剂免疫可溶性BST-1转基因小鼠（品系S15）和野生型小鼠（分别n=6和8），它们与DBA/1 J回交8代。虽然S15小鼠的关节炎发病率比野生小鼠增加。与DBA/1 J回交5代的BST-1 KO小鼠（N=15）在第57天关节炎发病率高于野生小鼠（n=13）（分别为100%和69%）。严重程度无差异。BST-1在胶原诱导的关节炎中没有重要作用。(2)BST-1/CD 38双基因敲除小鼠的制备：筛选CD 38和BST-1双基因敲除的ES细胞克隆，获得嵌合小鼠。对F1代小鼠的分析表明，通过杂交F1代小鼠将获得成功靶向CD 38和BST-1基因的小鼠。(3)受体功能：BST-1在mBST-1BAF（用鼠BST-1 cDNA转染的前B细胞系）表面的交联导致细胞聚集，表明通过BST-1的信号诱导细胞粘附。(4)BST-1配体：从结合BST-1的B细胞系制备用于表达克隆的cDNA文库。经2 × 10 ~（14）个克隆筛选，未获得人BST-1配体的候选cDNA。

项目成果

Itoh M.et al.: "Deletion of bone marrow stromal cell antigen-1(CD157) gene impaired systemic thym us independent-2 antigen-induced IgG3 and mucosal TD antigen-elicited Ig A responses"J.Immunol.. 161. 3974-3983 (1998)

Itoh M.et al.：“删除骨髓基质细胞抗原 1 (CD157) 基因会损害全身胸腺 us 独立 2 抗原诱导的 IgG3 和粘膜 TD 抗原引发的 Ig A 反应”J.Immunol.. 161. 3974

Ishihara, K. et al.: "BST-1/CD157 regulates the humoral immune responses in vivo"75. 235-255 (2000)

Ishihara, K. 等人：“BST-1/CD157 调节体内体液免疫反应”75。

Sato,A,et al.: "Novel peptide inhibitor of ecto-ADP-ribosyl cyclase of bone marrow stromal cell antigen-1(BST-1/CD157)" Biochem.J.337. 491-496 (1999)

Sato,A,et al.：“骨髓基质细胞抗原 1 (BST-1/CD157) 胞外 ADP-核糖基环化酶的新型肽抑制剂”Biochem.J.337。

Shimaoka, Y., et al.: "Nurse-like cells from bone marrow and synovium of patients with rheumatoid arthritits promote survival and enhance function of human B cells"102. 606-618 (1998)

Shimaoka, Y. 等人：“来自类风湿关节炎患者骨髓和滑膜的护士样细胞可促进人类 B 细胞的存活并增强其功能”102。

Sato, A., et al.: "Novel peptide inhibitor of ecto-ADP-ribosyl cyclase of bone marrrow stromal cell antigen-1(BST-1/CD157)"337. 491-496 (1999)

Sato, A. 等人：“骨髓基质细胞抗原 1 (BST-1/CD157) 的外 ADP-核糖基环化酶的新型肽抑制剂”337。