调节性B细胞PPT课件

.,1,Bregs-RegulatoryBcells,.,Introduction,1,CluestoBregsexistence,2,Developmentanddifferentiation,3,4,Contents,PhenotypicalIdentification,6,Bregsindiseases,FunctionofBregs,5,.,Introduction,Traditionally,BcellshavebeenthoughttocontributetodiseasethroughproductionofantibodiesInthepasttwodecades,investigatorshaveattributedadditionalfunctionstoBcells,includingantigenpresentation,theproductionofmultiplecytokinesRecently,theabilityofBcellstonegativelyregulatecellularimmuneresponsesandinflammationhasbeendescribedandtheconceptofregulatoryBcellshasemerged.,.,CluestoBregsexistence,2002,BcellssuppressDTH,IL-10-producingBcellsregulateautoimmunityCD19+CD1dhiBcellsproducingIL-10controlTh2-drivencolitis,theterm“regulatoryBcells”,whichdefinesB-cellsubsetswithregulatoryproperties,wasfirstintroduced,BcelldecientmicedevelopchronicEAE,Bcellscouldrestraintheseverityofautoimmunedisease,1980,antigen-activatedBcellscouldinducetoleranceinrecipientnaivemice,SupportasuppressiveframeworkforBcellsandintroducealinkwithT-celltolerance,.,DevelopmentandDifferentiation,在骨髓发育，分布外周淋巴器官，参与特异性免疫,定位于大网膜、胸腔及肠黏膜固有层，参与非特异性免疫,.,DevelopmentandDifferentiation,FOBcell,T2MZPBcell,MZBcell,LeBienTW,TedderTF.Blymphocytes:howtheydevelopandfunction.Blood.2008,.,DevelopmentandDifferentiation,.,DevelopmentandDifferentiation,MauriC,EhrensteinMR.TheshorthistoryofregulatoryBcells.TrendsImmunol.2008,.,DevelopmentandDifferentiation,MauriC,EhrensteinMR.TheshorthistoryofregulatoryBcells.TrendsImmunol.2008,.,DevelopmentandDifferentiation,MizoguchiA,BhanAK.AcaseforregulatoryBcells.JImmunol.2006,.,PhenotypicalIdentification,HeY.TherolesofregulatoryBcellsincancer.JImmunolRes.2014.,.,PhenotypicalIdentification,MauriC.ImmuneregulatoryfunctionofBcells.AnnuRevImmunol.2012,.,PhenotypicalIdentification,MauriC.ImmuneregulatoryfunctionofBcells.AnnuRevImmunol.2012,.,PhenotypicalIdentification,BodhankarS.IL-10-producingB-cellslimitCNSinflammationandinfarctvolumeinexperimentalstroke.MetabBrainDis.2013,.,PhenotypicalIdentification,Thereisnouniquemarker,orsetofmarkers,thatexclusivelyidentifiestheBregsThereisnomasterregulatortranscriptionfactoridentifiedinBregdevelopmentIL-10secretionisstillavitalstandardintheidentificationofBregs,.,FunctionofBregs,MizoguchiA,BhanAK.AcaseforregulatoryBcells.JImmunol.2006,.,FunctionofBregs,MauriC.ImmuneregulatoryfunctionofBcells.AnnuRevImmunol.2012,.,FunctionofBregs,MauriC.ImmuneregulatoryfunctionofBcells.AnnuRevImmunol.2012,.,MauriC.ImmuneregulatoryfunctionofBcells.AnnuRevImmunol.2012,FunctionofBregs,.,Bregsinautoimmunity,Experimentalautoimmuneencephalomyelitis(EAE)InflammatoryBowelDisease(IBD)RheumatoidArthritis(RA),.,BregsinautoimmunityEAE,B-cell-deficientmice(mMT)failedtocontrolEAE,andunlikethewild-typemice,didnotundergospontaneousremission,IntheabsenceofIL-10productionbyBcells,thepro-inflammatorytype1immuneresponsepersistedandmicedidnotrecover,LackofdiseaseresolutionwasattributedtotheinabilityofTcellstoswitchtoaprotectiveTh2response,.,BregsinautoimmunityIBD,mMTTCRa-/-micemanifestanearlieronsetofdiseaseandanexacerbatedintestinalinammationcomparedwiththeTCRa-/-mice,Theameliorationofdiseasewasparalleledbyanincreaseintheclearanceofapoptoticcells,suggestinganautoantibody-mediatedprotectivemechanism,AdministrationofpurifiedimmunoglobulinfromTCRa-/-micewithamixtureofmonoclonalautoantibodiesattenuatecolitis,.,BregsinautoimmunityRA,StimulationofarthritogenicBcellswithanagonisticanti-CD40andcollagengeneratedasubsetofBcellsproducingIL-10,ThissuppressiveeffectwasassociatedwithadownregulationofTh1cytokinesandwasdependentuponthereleaseofIL-10,Transferofcollagenandanti-CD40-stimulatedBcellstosyngeneicimmunizedmicepreventedtheinductionofarthritisandamelioratedestablisheddisease,.,Bregsincancer,BregssupportlungmetastasesviaTreggeneration,OlkhanudPB.Tumor-evokedregulatoryBcellspromotebreastcancermetastasisbyconvertingrestingCD4+TcellstoT-regulatorycells.CancerRes.2011,.,Bregsincancer,BregssupportlungmetastasesviaTreggeneration,OlkhanudPB.Tumor-evokedregulatoryBcellspromotebreastcancermetastasisbyconvertingrestingCD4TcellstoT-regulatorycells.CancerRes.2011,.,Bregsincancer,RegulatoryBcellproductionofIL-10inhibitslymphomadepletionduringCD20immunotherapy,HorikawaM.RegulatoryBcellproductionofIL-10inhibitslymphomadepletionduringCD20immunotherapyinmice.JClinInvest.2011,.,BregsintransplantationGVHD,RoweV.HostBcellsproduceIL-10followingTBIandattenuateacuteGVHDafterallogeneicbonemarrowtransplantation.Blood.2006,AcuteGVHDisinitiallyaugmentedinmMTrecipientsrelativetowild-typerecipientsasaresultofanincreaseindonorT-cellproliferation,expansion,andinflammatorycytokineproduction,RecipientmiceinwhichBcellsareunabletoproduceIL-10developmoresevereacuteGVHDthanrecipientmiceinwhichBcellsarewildtype,TBIdepletemostBcellbutrapidlyinducessustainedinterleukin-10generationfromBcells,.,OutstandingquestionsandFuturuedirections,weneedtobetteridentifysurfacemarkersthat,coupledwithtranscriptionalfactors,wouldprovideauniquesignatureThequestionofwhetherallBcellsproducingIL-10,irrespectiveoftheirphenotype,arecapableofsuppressionorwhethermultipleBregsubsetsexistandiftheyareallequipollentisyettobedetermined,.,OutstandingquestionsandFuturuedirections,Weneedtobetteridentifysurfacemarkersthat,coupledwithtranscriptionalfactors,wouldprovideauniquesignatureThequestionofwhetherallBcellsproducingIL-10,irrespectiveoftheirphenotype,arecapableofsuppressionorwhethermultipleBregsubsetsexistandiftheyareallequipollentisyettobedetermined,.,OutstandingquestionsandFuturuedirections,TherearevirtuallynodatademonstratingwhetherBregsmigratetothesiteofinflammationandwhethertheyinteractinsi