Infantino Simona, Light Amanda, O'Donnell Kristy, Bryant Vanessa, Avery Danielle T, Elliott Michael, Tangye Stuart G, Belz Gabrielle, Mackay Fabienne, Richard Stephane, Tarlinton David
Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, 3052, Australia.
Department of Medical Biology, University of Melbourne, Parkville, Victoria, 3010, Australia.
Nat Commun. 2017 Oct 12;8(1):891. doi: 10.1038/s41467-017-01009-1.
Arginine methylation catalyzed by protein arginine methyltransferases (PRMT) is a common post-translational modification in mammalian cells, regulating many important functions including cell signalling, proliferation and differentiation. Here we show the role of PRMT1 in B-cell activation and differentiation. PRMT1 expression and activity in human and mouse peripheral B cells increases in response to in vitro or in vivo activation. Deletion of the Prmt1 gene in mature B cells establishes that although the frequency and phenotype of peripheral B cell subsets seem unaffected, immune responses to T-cell-dependent and -independent antigens are substantially reduced. In vitro activation of Prmt1-deficient B cells with a variety of mitogens results in diminished proliferation, differentiation and survival, effects that are correlated with altered signal transduction from the B cell receptor. Thus PRMT1 activity in B cells is required for correct execution of multiple processes that in turn are necessary for humoral immunity.PRMT1 is an arginine methyltransferase involved in a variety of cell functions. Here the authors delete PRMT1 specifically in mature B cells to show the importance of arginine methylation for B cell proliferation, differentiation and survival, and thereby for humoral immunity.
由蛋白质精氨酸甲基转移酶(PRMT)催化的精氨酸甲基化是哺乳动物细胞中一种常见的翻译后修饰,可调节包括细胞信号传导、增殖和分化在内的许多重要功能。在此,我们展示了PRMT1在B细胞活化和分化中的作用。人和小鼠外周B细胞中的PRMT1表达及活性会因体外或体内活化而增加。在成熟B细胞中删除Prmt1基因后发现,尽管外周B细胞亚群的频率和表型似乎未受影响,但对T细胞依赖性和非依赖性抗原的免疫反应却大幅降低。用多种有丝分裂原体外激活Prmt1缺陷型B细胞会导致增殖、分化和存活减少,这些效应与B细胞受体信号转导改变相关。因此,B细胞中的PRMT1活性对于正确执行多个过程是必需的,而这些过程反过来对于体液免疫也是必需的。PRMT1是一种参与多种细胞功能的精氨酸甲基转移酶。在此,作者专门在成熟B细胞中删除PRMT1,以显示精氨酸甲基化对B细胞增殖、分化和存活的重要性,进而对体液免疫的重要性。