Arginine methylation catalyzed by PRMT1 is required for B cell activation and differentiation

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作者
Simona Infantino
Amanda Light
Kristy O’Donnell
Vanessa Bryant
Danielle T. Avery
Michael Elliott
Stuart G. Tangye
Gabrielle Belz
Fabienne Mackay
Stephane Richard
David Tarlinton
机构
[1] Walter and Eliza Hall Institute of Medical Research,Department of Medical Biology
[2] University of Melbourne,Department of Immunology and Pathology
[3] Monash University,Immunology Division
[4] Garvan Institute of Medical Research,Sydney Medical School
[5] University of Sydney,Chris O’Brien Lifehouse Cancer Centre
[6] Royal Prince Alfred Hospital,St Vincent’s Clinical School, Faculty of Medicine
[7] University of NSW,Department of Microbiology and Immunology
[8] University of Melbourne,Lady Davis Institute for Medical Research
[9] McGill University,undefined
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摘要
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.
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