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; 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

Characterization of human anti-BAFF scFv-Fc that inhibits the activity of BAFF in vivo

摘要

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MTT、ELISA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。

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.

HTML全文

参考文献(0)

施引文献

资源附件(0)