调节性B细胞.ppt
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 Bcell de cientmicedevelopchronicEAE Bcellscouldrestraintheseverityofautoimmunedisease 1980 antigen activatedBcellscouldinducetoleranceinrecipientnaivemice Supporta suppressiveframework forBcellsandintroducealinkwithT 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 T2 MZPBcell MZBcell LeBienTW TedderTF Blymphocytes howtheydevelopandfunction Blood 2008 DevelopmentandDifferentiation DevelopmentandDifferentiation MauriC EhrensteinMR The short historyofregulatoryBcells TrendsImmunol 2008 DevelopmentandDifferentiation MauriC EhrensteinMR The short historyofregulatoryBcells 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 Bregsinautoimmunity EAE B cell deficientmice mMT failedtocontrolEAE andunlikethewild typemice didnotundergospontaneousremission IntheabsenceofIL 10productionbyBcells thepro inflammatorytype1immuneresponsepersistedandmicedidnotrecover LackofdiseaseresolutionwasattributedtotheinabilityofTcellstoswitchtoaprotectiveTh2response Bregsinautoimmunity IBD mMTTCRa micemanifestanearlieronsetofdiseaseandanexacerbatedintestinalin ammationcomparedwiththeTCRa mice Theameliorationofdiseasewasparalleledbyanincreaseintheclearanceofapoptoticcells suggestinganautoantibody mediatedprotectivemechanism AdministrationofpurifiedimmunoglobulinfromTCRa micewithamixtureofmonoclonalautoantibodiesattenuatecolitis Bregsinautoimmunity RA StimulationofarthritogenicBcellswithanagonisticanti CD40andcollagengeneratedasubsetofBcellsproducingIL 10 ThissuppressiveeffectwasassociatedwithadownregulationofTh1cytokinesandwasdependentuponthereleaseofIL 10 Transferofcollagenandanti CD40 stimulatedBcellstosyngeneicimmunizedmicepreventedtheinductionofarthritisandamelioratedestablisheddisease Bregsincancer BregssupportlungmetastasesviaTreggeneration OlkhanudPB Tumor evokedregulatoryBcellspromotebreastcancermetastasisbyconvertingrestingCD4 TcellstoT regulatorycells CancerRes 2011 Bregsincancer BregssupportlungmetastasesviaTreggeneration OlkhanudPB Tumor evokedregulatoryBcellspromotebreastcancermetastasisbyconvertingrestingCD4 TcellstoT regulatorycells CancerRes 2011 Bregsincancer RegulatoryBcellproductionofIL 10inhibitslymphomadepletionduringCD20immunotherapy HorikawaM RegulatoryBcellproductionofIL 10inhibitslymphomadepletionduringCD20immunotherapyinmice JClinInvest 2011 Bregsintransplantation GVHD RoweV HostBcellsproduceIL 10followingTBIandattenuateacuteGVHDafterallogeneicbonemarrowtransplantation Blood 2006 AcuteGVHDisinitiallyaugmentedinmMTrecipientsrelativetowild typerecipientsasaresultofanincreaseindonorT cellproliferation expansion andinflammatorycytokineproduction RecipientmiceinwhichBcellsareunabletoproduceIL 10developmoresevereacuteGVHDthanrecipientmiceinwhichBcellsarewildtype TBIdepletemostBcellbutrapidlyinducessustainedinterleukin 10generationfromBcells OutstandingquestionsandFuturuedirections weneedtobetteridentifysurfacemarkersthat coupledwithtranscriptionalfactors wouldprovideauniquesignatureThequestionofwhetherallBcellsproducingIL 10 irrespectiveoftheirphenotype arecapableofsuppressionorwhethermultipleBregsu
