首页|Dhx33 promotes B-cell growth and proliferation by controlling activation-induced rRNA upregulation
Dhx33 promotes B-cell growth and proliferation by controlling activation-induced rRNA upregulation
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Upon recognition of foreign antigens,naïve B cells undergo rapid activation,growth,and proliferation.How B-cell growth and proliferation are coupled with activation remains poorly understood.Combining 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 proliferation.Mutant mice with B-cell-specific deletion of Dhx33 exhibited impaired B-cell development,germinal center reactions,plasma cell differentiation,and antibody production.Dhx33-deficient B cells appeared normal in the steady state and early stage of activation but were retarded in growth and proliferation.Mechanistically,Dhx33 played an indispensable role in activation-induced upregulation of ribosomal DNA(rDNA)transcription.In 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 death.Our 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.
RNA helicasesB cell activationGerminal center reaction
State Key Laboratory of Cellular Stress Biology,School of Life Sciences,Faculty of Medicine and Life Sciences,Xiamen University,Xiamen,Fujian,China
Department of Immunology and Microbiology,The Scripps Research Institute,La Jolla,CA 92037,USA
Genentech Inc.,South San Francisco,CA 94080,USA
Sanofi Institute for Biomedical Research,Suzhou,Jiangsu 215123,China
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National Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaFundamental Research Funds for the Central Universities of China-Xiamen UniversitySanofi Institute for Biomedical Research(SIBR)
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