Initiation of plasma-cell differentiation is independent of the transcription factor Blimp-1
Initiation of plasma-cell differentiation is independent of the transcription factor Blimp-1
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DOI：
10.1016/j.immuni.2007.04.007
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发表时间：
2007-05-01
期刊：
影响因子：
32.4
通讯作者：
Nutt, Stephen L.
中科院分区：
文献类型：
--
作者：
Kallies, Axel;Hasbold, Jhagvaral;Nutt, Stephen L.
Blimp - 1被认为是B细胞终末分化为分泌抗体的浆细胞的关键调节因子。我们在此表明，用Prdm1（编码Blimp - 1的基因）的DNA结合缺陷型突变纯合子的胎肝细胞重建的Rag1（- / -）小鼠缺乏明确的浆细胞区室，但可检测到所有免疫球蛋白同种型的量。体外分析显示，Blimp - 1对于抗体分泌的起始不是必需的，但对于随后的高免疫球蛋白产生是必不可少的。不依赖Blimp - 1的分化在一个前浆母细胞阶段受阻，其特征是Pax5表达降低和浆细胞基因的激活。对Blimp - 1充足分化的分析揭示了在Blimp - 1表达之前的一个阶段，在此阶段，几个通常被Pax5抑制的基因被重新表达，这表明浆细胞分化是由Pax5功能的抑制所启动的。我们的结果表明，完全的浆细胞分化而非向浆细胞命运的定向需要功能性Blimp - 1的表达。
Blimp-1 is considered an essential regulator of the terminal differentiation of B cells into antibody-secreting plasma cells. We show here that Rag1(-/-) mice reconstituted with fetal liver cells homozygous for a DNA-binding-deficient mutant of Prdm1 (the gene encoding Blimp-1) lack a defined plasma-cell compartment, yet show detectable amounts of all immunoglobulin isotypes. In vitro analysis revealed that Blimp-1 is not required for the initiation of antibody secretion but is essential for subsequent high immunoglobulin production. Blimp-1-independent differentiation was blocked at a pre-plasmablast stage characterized by decreased Pax5 expression and the activation of plasma-cell genes. Analysis of Blimp-1-sufficient differentiation revealed a phase prior to Blimp-1 expression in which several genes normally repressed by Pax5 are re-expressed, suggesting that plasma-cell differentiation is initiated by the inhibition of Pax5 function. Our results indicate that full plasma-cell differentiation but not commitment to the plasma-cell fate requires the expression of functional Blimp-1.