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

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。

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

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.