Blimp-1 orchestrates plasma cell differentiation by extinguishing the mature B cell gene expression program
Blimp-1 orchestrates plasma cell differentiation by extinguishing the mature B cell gene expression program
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DOI：
10.1016/s1074-7613(02)00335-7
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发表时间：
2002-07-01
期刊：
影响因子：
32.4
通讯作者：
Staudt, LM
中科院分区：
文献类型：
--
作者：
Shaffer, AL;Lin, KI;Staudt, LM
BLIMP-1是一种转录抑制因子，驱动B细胞向浆细胞的终末分化。利用DNA微阵列，我们发现将Blimp-1引入B细胞可以阻止一组非常大的基因的表达，而诱导的基因数量要少得多。BLIMP-1通过直接抑制编码包括SPI-B和ID3在内的几种转录因子的基因来启动这种基因表达变化，这些转录因子通过B细胞受体调节信号。BLIMP-1还通过阻断AID、Ku70、Ku86、DNA-PKcs和STAT6的表达来抑制免疫球蛋白类的转换。这些发现表明，Blimp-1通过抑制对B细胞受体信号转导、生发中心B细胞功能和增殖重要的基因表达而促进浆细胞分化，同时允许XBP-1等重要浆细胞基因的表达。
Blimp-1, a transcriptional repressor, drives the terminal differentiation of B cells to plasma cells. Using DNA microarrays, we found that introduction of Blimp-1 into B cells blocked expression of a remarkably large set of genes, while a much smaller number was induced. Blimp-1 initiated this cascade of gene expression changes by directly repressing genes encoding several transcription factors, including Spi-B and Id3, that regulate signaling by the B cell receptor. Blimp-1 also inhibited immunoglobulin class switching by blocking expression of AID, Ku70, Ku86, DNA-PKcs, and STAT6. These findings suggest that Blimp-1 promotes plasmacytic differentiation by extinguishing gene expression important for B cell receptor signaling, germinal center B cell function, and proliferation while allowing expression of important plasma cell genes such as XBP-1.