药学学报, 2012, 47(10): 1336-1340
引用本文:
曹 萌, 曹 鹏, 张双全, 程 莹, 颜怀江. B淋巴细胞激活因子的全人源抗体对BAFF生物学活性的拮抗作用[J]. 药学学报, 2012, 47(10): 1336-1340.
CAO Meng, CAO Peng, ZHANG Shuang-quan, CHENG Ying, YAN Huai-jiang. Characterization of human anti-BAFF scFv-Fc that inhibits the activity of BAFF in vivo[J]. Acta Pharmaceutica Sinica, 2012, 47(10): 1336-1340.

B淋巴细胞激活因子的全人源抗体对BAFF生物学活性的拮抗作用
曹  萌1*, 曹  鹏2, 张双全3, 程  莹1, 颜怀江3
(1. 东南大学医学院病原生物学与免疫学系, 江苏 南京 210009; 2. 江苏省中药研究所, 江苏 南京 210028; 3. 南京师范大学生命科学学院, 江苏 南京 210046)
摘要:

通过注射人B淋巴细胞激活因子 (hsBAFF) 的全人源抗体scFv-Fc, 观察其对hsBAFF引发的B细胞增殖与分化的拮抗作用。将ICR小鼠随机分为对照组hsBAFF (1 mg·kg−1) 组、hsBAFF (1 mg·kg−1) + Ab (1 mg·kg−1) 组、hsBAFF (1 mg·kg−1) + Ab (2 mg·kg−1) 组、hsBAFF (1 mg·kg−1) + human IgG (1 mg·kg−1) 组和hsBAFF (1 mg·kg−1) + human IgG (2 mg·kg−1) 组。采用MTTELISA及流式细胞检测, 分别考察各组小鼠脾脏指数、脾脏B淋巴细胞增殖活性及成熟分化和血浆中抗体水平。结果表明: 通过注射scFv-Fc有效抑制了hsBAFF引起的脾脏B细胞增殖以及血浆中抗体水平的升高; 同时scFv-Fc也显著抑制了hsBAFF引发的B细胞成熟分化, 具有潜在的抗体药物开发价值。

关键词:   
Characterization of human anti-BAFF scFv-Fc that inhibits the activity of BAFF in vivo
Abstract:

To investigate the effects of human anti-BAFF scFv-Fc against the hsBAFF, ICR mice were randomly divided into six groups: control, hsBAFF (1 mg·kg−1), hsBAFF (1 mg·kg−1) + Ab (1 mg·kg−1), hsBAFF (1 mg·kg−1) + Ab (2 mg·kg−1), hsBAFF (1 mg·kg−1) + human IgG (1 mg·kg−1) and hsBAFF (1 mg·kg−1) + human IgG (2 mg·kg−1) groups.  The effects of scFv-Fc administration on the proliferation of B lymphocytes were evaluated using an MTT assay.  The titres of antibody in the serum and B lymphocytes differentiation were assessed by ELISA and flow cytometry, respectively.  The results showed that administration of scFv-Fc to mice injected with hsBAFF significantly prevented human BAFF-induced increases in splenic B cell numbers and serum immunoglobulin levels.  Furthermore, this fully human antibody would avoid inducing the human anti-mouse antibody (HAMA) response when used in humans.  These findings suggest that the compact antibody may be useful in therapeutic or diagnostic application of the BAFF-associated autoimmune diseases in human.

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