Blimp1-BCMA调控浆细胞功能在系统性红斑狼疮发病中的意义

【摘要】 目的 探讨Blimp1在MRL/lpr狼疮鼠中的表达水平，为靶向浆细胞治疗SLE提供思路。方法用EMSA和CHIP证实Blimp1对B细胞成熟抗原（BCMA）的调控作用，并用实时定量PCR检测MRL/lpr狼疮鼠与正常鼠脾脏和淋巴结中Blimp1mRNA的表达差异。结果 Blimp1能与BCMA基因启动子相结合。狼疮鼠组脾脏Blimp1mRNA的相对表达水平高于正常对照组Blimp1mRNA的相对表达水平（Z = 2.609，P < 0.01），狼疮鼠组淋巴结中Blimp1的相对表达水平也高于正常对照组Blimp1mRNA的相对表达水平（ Z = 3.402，P < 0.01），差异有统计学意义。结论 BCMA可能是Blimp1的靶基因，Blimp1可直接调控BCMA表达，在维持浆细胞存活及抗体分泌中发挥作用。 【关键词】 红斑狼疮，系统性； Blimp1； B细胞成熟抗原； 浆细胞； 小鼠，近交MRL lpr

Roles of regulation of plasma cell function by Blimp1-B cell maturation antigen in the pathogenesis of systemic lupus erythematosus

PENG Xue-biao, OU Li-na. Department of Dermatology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, ChinaCorresponding author: PENG Xue-biao, Email: pengxuebiao@126.com 【Abstract】 Objective To detect the expression of Blimp1 gene in MRL/lpr mice, so as to provide new ideas for plasma cell-targeting therapy of systemic lupus erythematosus （SLE）. Methods Electrophoretic mobility shift assay （EMSA） and chromatin immunoprecipitation analysis （ChIP） were performed to evaluate the regulatory effect of Blimp1 on B cell maturation antigen （BCMA）, and fluorescence-based quantitative PCR was carried out to detect the expression of Blimp1 mRNA in spleen and lymph node tissue of MRL/lpr mice and normal control mice. The intergroup difference in Blimp1 mRNA expression was assessed by rank sum test. Results Blimp1 could bind to the BCMA gene promoter. Increased Blimp1 mRNA expression was observed in both the spleen and lymph node tissue of MRL/lpr mice compared with the normal control mice （Z = 2.609, 3.402, respectively, both P < 0.01）. Conclusions BCMA appears to be the target gene of Blimp1, and Blimp1 may plays a certain role in the maintenance of plasma cell survival and antibody production via directly regulating BCMA gene expression. 【Key words】 Lupus erythematosus, systemic; Blimp1; B-cell maturation antigen; Plasma cell; Mice, inbred MRL lpr