Dhx33 promotes B-cell growth and proliferation by controlling activation-induced rRNA upregulation
作者机构:state Key Laboratory of Cellular Stress BiologySchool of Life SciencesFaculty of Medicine and Life SciencesXiamen UniversityXiamenFujianChina Department of Immunology and MicrobiologyThe Scripps Research InstituteLa JollaCA 92037USA Genentech Inc.South San FranciscoCA 94080USA Sanof Institute for Biomedical ResearchSuzhoujiangsu 215123China
出 版 物:《Cellular & Molecular Immunology》 (中国免疫学杂志(英文版))
年 卷 期:2023年第20卷第3期
页 面:277-291页
核心收录:
学科分类:1001[医学-基础医学(可授医学、理学学位)] 100102[医学-免疫学] 10[医学]
基 金:the National Natural Science Foundation of China(31570882,31770950 and 32070877 to W-H.L,and 81961138008 to CX) the Fundamental Research Funds for the Central Universities of China-Xiamen University(20720170064 to CX) the Sanofi Institute for Biomedical Research(SIBR)
主 题:RNA helicases B cell activation Germinal center reaction
摘 要:Upon recognition of foreign antigens,naïve B cells undergo rapid activation,growth,and *** B-cell growth and proliferation are coupled with activation remains poorly *** CRISPR/Cas9-mediated functional analysis and mouse genetics approaches,we found that Dhx33,an activation-induced RNA helicase,plays a critical role in coupling B-cell activation with growth and *** mice with B-cell-specific deletion of Dhx33 exhibited impaired B-cell development,germinal center reactions,plasma cell differentiation,and antibody ***33-deficient B cells appeared normal in the steady state and early stage of activation but were retarded in growth and ***,Dhx33 played an indispensable role in activation-induced upregulation of ribosomal DNA(rDNA)*** the absence of Dhx33,activated B cells were compromised in their ability to ramp up 47S ribosomal RNA(rRNA)production and ribosome biogenesis,resulting in nucleolar stress,p53 accumulation,and cellular *** findings demonstrate an essential role for Dhx33 in coupling B-cell activation with growth and proliferation and suggest that Dhx33 inhibition is a potential therapy for lymphoma and antibody-mediated autoimmune diseases.