Tellier Julie, Shi Wei, Minnich Martina, Liao Yang, Crawford Simon, Smyth Gordon K, Kallies Axel, Busslinger Meinrad, Nutt Stephen L
The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.
Department of Medical Biology, The University of Melbourne, Parkville, Australia.
Nat Immunol. 2016 Mar;17(3):323-30. doi: 10.1038/ni.3348. Epub 2016 Jan 18.
Plasma cell differentiation requires silencing of B cell transcription, while it establishes antibody-secretory function and long-term survival. The transcription factors Blimp-1 and IRF4 are essential for the generation of plasma cells; however, their function in mature plasma cells has remained elusive. We found that while IRF4 was essential for the survival of plasma cells, Blimp-1 was dispensable for this. Blimp-1-deficient plasma cells retained their transcriptional identity but lost the ability to secrete antibody. Blimp-1 regulated many components of the unfolded protein response (UPR), including XBP-1 and ATF6. The overlap in the functions of Blimp-1 and XBP-1 was restricted to that response, with Blimp-1 uniquely regulating activity of the kinase mTOR and the size of plasma cells. Thus, Blimp-1 was required for the unique physiological ability of plasma cells that enables the secretion of protective antibody.
浆细胞分化需要沉默B细胞转录，同时建立抗体分泌功能和长期存活能力。转录因子Blimp-1和IRF4对浆细胞的产生至关重要；然而，它们在成熟浆细胞中的功能仍不清楚。我们发现，虽然IRF4对浆细胞的存活至关重要，但Blimp-1对此并非必需。缺乏Blimp-1的浆细胞保留了它们的转录特征，但失去了分泌抗体的能力。Blimp-1调节未折叠蛋白反应（UPR）的许多成分，包括XBP-1和ATF6。Blimp-1和XBP-1功能的重叠仅限于该反应，Blimp-1独特地调节激酶mTOR的活性和浆细胞的大小。因此，Blimp-1是浆细胞独特生理能力所必需的，这种能力使保护性抗体得以分泌。
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