中文摘要：

考察含对硝基苯丙氨酸的 B 淋巴细胞刺激因子（ BAFF）治疗 BAFF过表达的自身免疫性疾病的效果.利用本研 究前期构建的工程菌,表达纯化了 B 淋巴细胞刺激因子的可溶型突变体（ smBAFF）以及在其6 5位定点引入了对硝基苯丙 氨酸的改构体（/）N02Phe65SmBAFF） D 通过考察/）N02Phe65SmBAFF体外促小鼠淋巴细胞增殖活性、免疫原性以及所诱导的 抗血清对天然BAFF活性的抑制作用,评价了其用于治疗BAFF过表达的自身免疫性疾病的可行性;同时采用了 cGVHD （ graft-versus-host disease）诱导的狼疮腎炎小鼠模型评价了 N02Phe65 smBAFF的药理活性.结果表明：定点引入了对硝基 苯丙氨酸的/）N02Phe65SmBAFF不具有促进小鼠淋巴细胞增殖的能力;由于对硝基苯丙氨酸的引入显著增强了蛋白的免疫 原性,诱导机体产生了可以抑制天然BAFF活性的交叉抗体;在cGVHD诱导的狼疮肾炎小鼠模型中,N02Phe65SmBAFF可 显著减轻疾病症状.定点引入了对硝基苯丙氨酸的/）N02Phe65SmBAFF可以作为治疗BAFF过表达的自身免疫性疾病的候选分子.

英文摘要：

In order to verify whether j9-nitrophenylalanine-containing BAFF vaccine can be used as a candidate molecule for the treatment of autoimmune diseases with BAFF over-expression, a soluble mutant of B cell activa-ting factor belonging to the TNF Family （ smBAFF） and its j9N02Phe mutant（j9N02Phe65 smBAFF）, which site specific incorporated j9N02Phe at position 65 of smBAFF, were expressed and purified. In order to evaluate the feasibility of using j9N02Phe65 smBAFF to treat BAFF-over-expressed autoimmune diseases, we investigate its Lymphocyte-stimulating capacity, immunogenicity and inhibitory effect of serum on biological activity of natural BAFF. The pharmacological activity of j9N02Phe65 smBAFF was evaluated using a cGVHD （ graft-versus-host dis-ease） induced SLE mouse model. Results indicated that j9N02Phe65 smBAFF, could bind to mouse lymphocytes but could not promote the proliferation of mouse lymphocytes. Moreover, the incorporation of j9N02Phe significantly increased the immunogenicity and induced cross-antibody, which can inhibit the biological activity of naturalBAFF. In cGVHD induced SLE mouse model, j9N02Phe65 smBAFF can significantly reduce the symptoms of the disease and play a therapeutic role. Therefore, j9N02Phe65 smBAFF can be used as a candidate molecule for the treatment of autoimmune diseases with BAFF over-expression.