Active inhibition of plasma cell development in resting B cells by microphthalmia-associated transcription factor.

Active inhibition of plasma cell development in resting B cells by microphthalmia-associated transcription factor.
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DOI:
10.1084/jem.20040612
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发表时间:
2004-07-05
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Peng SL
Peng SL
中科院分区:
其他
文献类型:
--
作者:
Lin L;Gerth AJ;Peng SL

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B细胞终末分化涉及到向抗体分泌浆细胞的发育,反映了原浆细胞转录调节因子的协同激活,如Blimp-1, IRF-4和Xbp-1。在这里,我们发现小眼相关转录因子(Mitf)在幼稚B细胞中高度表达,它通过抑制IRF-4来对抗终末分化过程。Mitf活性缺陷导致自发B细胞活化、抗体分泌和自身抗体产生。相反,异位Mitf表达抑制IRF-4、浆细胞标志物CD138的表达和抗体分泌。因此,Mitf通过抑制抗体分泌命运来调节B细胞稳态。
B cell terminal differentiation involves development into an antibody-secreting plasma cell, reflecting the concerted activation of proplasma cell transcriptional regulators, such as Blimp-1, IRF-4, and Xbp-1. Here, we show that the microphthalmia-associated transcription factor (Mitf) is highly expressed in naive B cells, where it antagonizes the process of terminal differentiation through the repression of IRF-4. Defective Mitf activity results in spontaneous B cell activation, antibody secretion, and autoantibody production. Conversely, ectopic Mitf expression suppresses the expression of IRF-4, the plasma cell marker CD138, and antibody secretion. Thus, Mitf regulates B cell homeostasis by suppressing the antibody-secreting fate.
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