B細(xì)胞及其新型免疫調(diào)節(jié)功能研究ProliferationAntibodiessecretionBCRCD19B-cellT-cellPCCD40L-CD40B-cell

isaneffector

cell……butalsoaregulatory

cellInhibitionofCD80,CD86,HLAInhibitionofl’IL12InductionofTregInhibitionofIFNγ,TNFαnTreg,iTregNKTregBregDCDCTCD4+IL-10CD1dIL-10IL-10,TGFβAnergyTCD8+TGFβ1IL-10TCD4+InhibitionofproliferationIL-10AutoimmunediseasesAntitumorImmunityTransplantationAllergiesJamin,ArthritisRheum.2008Bregsinmice,IL-10isthekeyPhenotypesofIL-10producingBregsinmiceILBsB2“Innate”Bregs“Immature”Bregs“Adaptive”BregsIgMIL-10BCR/CD40/(TLR)IgMTLRLs/microbesCD40ligation?ILBsT2-MZPIL-10IL-10T2-MZP?Bregclassification?Zhang,CMI,2013ILBsB2“Innate”Bregs“Immature”Bregs“Adaptive”BregsIgMIL-10BCR/CD40/(TLR)IgMTLRLs/microbesCD40ligation?ILBsT2-MZPIL-10T2-MZP?Innate-likeBcell-derivedBregs?IL-10BregclassificationZhang,CMI,2013PartI:InnateneonatalBreginmiceandhumansPartII:HumanBcellprojectPartI:InnateneonatalBreginmiceandhumansPartII:HumanBcellprojectMouseBcellsubsetontogenyHardyetal.,2006CD5+IL-10+BonemarrowLiverB2Marginalzone(MZ)BB1CD5+ConventionalBInnate-likeBIL-10-producingneonatalCD5+Bcellsinmice-CD19+CD19+CD5+CD5-Invivo,neonatalCD5+BcellsprotectfromlethalinflammationCpGTNF-

IL-10NeoBsubsetsNeopDC+48hCD5+CD5-IL-10-/-

pDC:

+-+-+-+Bcell:-TNF-

(pg/ml)IL-10(ng/ml)NeonatalCD5+Bcell-derivedIL-10controls

pDC

response

following

CpGstimulation

CpG+CTKIL-10NeoBcellspDC-derivedtypeIIFNs

enhanceIL-10productionbyneonatalBcells

following

CpGstimulationIFN-

/Developmentalregulationofinflammation?HighpercentageofCD5+BcellsincordbloodAduNeoCD45+CD20+CD20+TLR7TLR9TLR9HumanneonatalBcellsproducemuchhigheramountofIL-10thanadultnon-memoryBcellsfollowingTLRstimulationsIFN-

promotesIL-10productionfromBcellsfollowingTLRtriggeringIFN-aStudythecross-talkbetween

human

pDCandBcellspDC

enhancethecapacityofIL-10productionbyBcells

followingTLRactivationIL-10BaloneBpDCFrompDC+Bco-cultureCpGCstimulationEffectofBcellsonThdifferentiationcapacityofpDCpDC48hCpGC+/-aIL-10FACS-sortedpDCAllogenicCD4+na?veT6daysPMA/IonomycinICSpDC+BNeonatalBcells

negativelycontrolTh1-primingcapacityofpDC

following

CpGstimulationinanIL-10-dependentmannerAduBIsneonatal

Breg

activity

associated

withaparticular

subset?Isneonatal

Breg

activity

associated

withaparticular

subset?InnateBregNeonatalCD5hiBcells

inhibitTh1-primingcapacityofpDC

following

CpGstimulationpDC48hCpGCFACS-sortedpDCAllogenicCD4+na?veT6daysPMA/IonomycinICSpDC+BsubsetpDC10+5hi5+5-IFN-gCD43CD27CD9CD44CD10+CD5hiCD5+CD5-ILT3SurfacemarkersofneonatalBsubsetsStudyofBcell

replication

historyAdultBcellsNeonatalBcellsInnateBregStudyofBcellVDJrepertoireandCDR3lengthCD5hi

BregshaveaJH4D6preferenceCD10+CD5hi

BregsshowaninhibitorysignatureNeonatal

regulationofimmuneresponsesBeneficial?Harmful?BCD5+TLR-LInflammationIL-12TNF-

(IL-6...)IFN-

/IL-10DCTLR-LpDCcDCMyeloidIL-10Pathogens?Pathogens?IFN-

/

PartI:InnateneonatalBreginmiceandhumansPartII:HumanBcellprojectCD19+PlasmablastBcellSwitchedBmemoryNon-switchedBBimmatureIgM+BmemoryBnaiveBcellsubsetsinadulthumanblood*:HumanBcellimmunobiologyislargelyunexplored*:AnintegrativeviewofhumanBcellsubsetswillbevaluabletodeciphertheirfunctionsIgM/DFITCIgGAEQdot655CD19BV605CD20A780CD5APCCD21P710CD24BV421CD27PECy7CD38A700CD43BV510HLADRBV785

CD70PC594CD95BV711FcRL4PECD3/33/56PECy515-colorflowcytometrytodefinehumanBcellsubsetsandtheirfunctionalstatusBDFortessaBLineageDevelopmentFunctionalHumanBcellsubsetdelineationStudyofhumanBcellsinadiseaseconditionSystemiclupuserythematosus,SLESLEaffects70per100,000inChinaBcellsCD38CD24HDSLEPatient1SLEPatient2BcellcompartmentisseverelyanddiverselydisturbedinSLEpatientsIL-6-producingBcellsweregreatlyincreasedinactiveSLEpatientsIL-6PMA+IonomycinstimulationHDActiveSLEResolvedSLESSCIL-10-producingBcellswerebarelydetectableIL-6-producingBcellsweregreatlyincreasedinactiveSLEpatientsPMA+IonomycinstimulationHDActiveSLEResolvedSLESwitchedmemoryBIgM+memoryBNa?veBOngoingBcellprojectinSLEpatients*:DetailedanalysisofBcellphenotypesindifferenttypesofSLEpatients*:RegulatoryfunctionsandunderlyingmechanismofdifferentBcellsubsets*:IdentificationofnovelBcell-relatedprognosticbiom