CD30 influences germinal center B-cell dynamics and the expansion of IgG1-switched B cells  

作　　者：Yan Wang Ursula Rambold Petra Fiedler Tea Babushku Claas L.Tapken Kai P.Hoefig Thomas P.Hofer Heiko Adler AliÖnder Yildirim Lothar J.Strobl Ursula Zimber-Strobl 

机构地区：[1]Research Unit Gene Vectors,Research Group B-Cell Development and Activation,Helmholtz Center Munich,German Research Center for Environmental Health,Munich,Germany [2]Institute of Asthma and Allergy Prevention,Helmholtz Center Munich,German Research Center for Environmental Health,Neuherberg,Germany [3]Member of the German Center of Lung Research(DZL),Munich,Germany [4]Institute of Lung Health and Immunity(LHI),Helmholtz Center Munich,Comprehensive Pneumology Center(CPC-M),Neuherberg,Germany [5]Research Unit Molecular Immune Regulation,Helmholtz Center Munich,Munich,Germany [6]Immunoanalytics-Research Group Tissue Control of Immunocytes,Helmholtz Center Munich,Munich,Germany [7]Walther Straub Institute of Pharmacology and Toxicology,Ludwig-Maximilians-University Munich,Munich,Germany [8]These authors contributed equally:Yan Wang,Ursula Rambold

出　　处：《Cellular & Molecular Immunology》2024年第12期1410-1425,共16页中国免疫学杂志(英文版)

基　　金：supported by the Deutsche Krebshilfe,Nr.70113859 to U.Z.-S.and H.A.,the Wilhelm-Sander-Stiftung Nr.2022.128.1 to A.Ö.Y and U.Z.-S.and the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under award number R01AI170965。

摘　　要：Initially,identified as a Hodgkin lymphoma marker,CD30 was subsequently detected on a subset of human B cells within and around germinal centers(GCs).While CD30 expression is typically restricted to a few B cells,expansion of CD30-expressing B cells occurs in certain immune disorders and during viral infections.The role of CD30 in B cells remains largely unclear.To address this gap in knowledge,we established a conditional CD30-knockin mouse strain.In these mice,B-cell-specific CD30 expression led to a normal B-cell phenotype in young mice,but most aged mice exhibited significant expansion of B cells,T cells and myeloid cells and increased percentages of GC B cells and IgG1-switched cells.This may be driven by the expansion of CD4+senescence-associated T cells and T follicular helper cells,which partially express CD30-L(CD153)and may stimulate CD30-expressing B cells.Inducing CD30 expression in antigen-activated B cells accelerates the GC reaction and augments plasma cell differentiation,possibly through the posttranscriptional upregulation of CXCR4.Furthermore,CD30 expression in GC B cells promoted the expansion of IgG1-switched cells,which displayed either a GC or memory-like B-cell phenotype,with abnormally high IgG1 levels compared with those in controls.These findings shed light on the role of CD30 signaling in GC B cells and suggest that elevated CD30+B-cell numbers lead to pathological lymphocyte activation and proliferation.

关 键 词：B lymphocytes Germinal center reaction CD30 Conditional mice CD30L Senescence associated T cells(SAT cells) 

分 类 号：R392[医药卫生—免疫学]