抑制Blimp-1表达导致浆细胞去分化  

Knockdown of Blimp-1 expression results in plasma cell dedifferentiation

作　　者：邓少丽[1] 胡福泉[1] 蹇锐[1] 蒋静[1] 程小星[1] 

机构地区：[1]第三军医大学基础医学部微生物学教研室,重庆400038

出　　处：《免疫学杂志》2006年第2期141-146,共6页Immunological Journal

基　　金：国家自然科学基金资助项目(30370603)

摘　　要：目的探讨转录因子Blimp-1在浆细胞发育中的作用。方法应用慢病毒载体稳定表达针对Blimp-1的siR-NA,抑制骨髓瘤细胞J558L中Blimp-1的表达。采用免疫荧光及流式细胞技术观察Blimp-1抑制前后细胞的免疫表型变化,半定量RT-PCR检测XBP-1J、-chainc、-myc、BCMA的变化。结果Blimp-1抑制后,浆细胞表面标志CD138表达显著下降,B淋巴细胞免疫标志CD19表达增加。同时,与浆细胞功能及存活密切相关的XBP-1、J-chain、BCMA基因表达下降,而促进B淋巴细胞增殖发育的c-myc表达上升。结论浆细胞中Blimp-1被抑制后,浆细胞发育程序出现再编程,发生了去分化现象,返回到更早期的发育阶段,提示Blimp-1特异性shRNA有可能用于浆细胞相关疾病的治疗。Objective To study the role of transcription factor Blimp-1 in plasma cell dedifferentiation. Methods The lentivirus vector expressing small interference RNA （siRNA） was constructed to repress the Blimp-1 gene expressions in J558L cell. The immunophenotype, XBP-1, J-chain, c-myc, and BCMA expressions were observed after repression of Blimp-1 expression. Results Compared with control, J558L cells stably transfected with Blimp-1-targeting shRNA vector showed significantly reduce of Blimp-1 expression. Immunotluorescent staining and flow cytometry analysis showed that inhibition of Blimp-1 expression in J558L cells is accompanied with reduce of CD138 （Syndecan-1） expression and reappearance of CD19 expression. The XBP-1, J-chain, and BCMA gene expressions were decreased and c-myc gene expression was elevated following knockdown of Blimp-1 expression in JSSSL ceils. Conclusion The results indicate that knockdown of Blimp-1 expression could induce reprogramming and dedifferentiation of plasma cells, thus Blimp-1-taigeting shRNA might be used to treat plasma cell-associated diseases.

关 键 词：BLIMP-1 浆细胞 细胞发育 BCMA RNA干扰 

分 类 号：R392[医药卫生—免疫学]