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

作　　者：曹萌[1] 曹鹏 张双全[3] 程莹[1] 颜怀江[3] 

机构地区：[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

出　　处：《药学学报》2012年第10期1336-1340,共5页Acta Pharmaceutica Sinica

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(1mg.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。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.

关 键 词：B淋巴细胞激活因子 人源性抗体 自身免疫性疾病 免疫治疗 

分 类 号：R963[医药卫生—微生物与生化药学]