B细胞及其新型免疫调节功能研究ProliferationAntibodiessecretionBCRCD19B-cellT-cellPCCD40L-CD40B-cellisaneffectorcell……butalsoaregulatorycellInhibitionofCD80,CD86,HLAInhibitionofl’IL12InductionofTregInhibitionofIFNγ,TNFαnTreg,iTregNKTregBregDCDCTCD4+IL-10CD1dIL-10IL-10,TGFβAnergyTCD8+TGFβ1IL-10TCD4+InhibitionofproliferationIL-10AutoimmunediseasesAntitumorImmunityTransplantationAllergiesJamin,ArthritisRheum.2008Bregsinmice,IL-10isthekeyPhenotypesofIL-10producingBregsinmice200220052007200820092009201020102010201020112011EAEinµMTmiceChroniccolitisinTCRα-/-miceNewbornmiceSLEinPNmiceCHSinCD19-/-miceCIAinDBA/1miceCHSinCD19-/-andhCD19TgmiceSLEinMRL/lprmiceEAEinC57BL/6miceAllergyandEAEinBALB/cetC57BL/6miceAllergyinBALB/candC57BL/6miceEAEinC57BL/6miceSLEinNZB/WmiceUlcerativecolitisinC57BL/6miceAIAdansdessourisµMT/B6miceaucunCD21intCD23+CD1dhiB-1B-cells:CD19hiCD5+IgMhiCD1d+MZB-cells:CD21hiCD23-CD21hiCD23loT2-MZP:CD21hiCD23+IgMhiIgD+CD1d+B10:CD1dhiCD5+T2-MZP:CD21hiCD23+CD93+CD24+CD1d+CD1d+CD21+CD22+CD23+CD24+IgD+IgM+CD19+CD23hiCD19+CD21hiCD23+IgMhiIgD+CD1dhiB10:CD1dhiCD5+B10:CD1dhiCD5+B10:CD1dhiCD5+T2-MZP:CD19+CD21hiCD23+CD24+YearModelPhenotypeILBsB2“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,2013•PartI:InnateneonatalBreginmiceandhumans•PartII:HumanBcellproject•PartI:InnateneonatalBreginmiceandhumans•PartII: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-10controlspDCresponsefollowingCpGstimulationCpG+CTKIL-10NeoBcellspDC-derivedtypeIIFNsenhanceIL-10productionbyneonatalBcellsfollowingCpGstimulationIFN-Developmentalregulationofinflammation?HighpercentageofCD5+BcellsincordbloodAduNeoCD45+CD20+CD20+TLR7TLR9TLR9HumanneonatalBcellsproducemuchhigheramountofIL-10thanadultnon-memoryBcellsfollowingTLRstimulationsIFN-promotesIL-10productionfromBcellsfollowingTLRtriggeringIFN-aStudythecross-talkbetweenhumanpDCandBcellspDCenhancethecapacityofIL-10productionbyBcellsfollowingTLRactivationIL-10BaloneBpDCFrompDC+Bco-cultureCpGCstimulationEffectofBcellsonThdifferentiationcapacityofpDCpDC48hCpGC+/-aIL-10FACS-sortedpDCAllogenicCD4+naïveT6daysPMA/IonomycinICSpDC+BNeonatalBcellsnegativelycontrolTh1-primingcapacityofpDCfollowingCpGstimulationinanIL-10-dependentmannerAduBIsneonatalBregactivityassociatedwithaparticularsubset?IsneonatalBregactivityassociatedwithaparticularsubset?InnateBregNeonatalCD5hiBcellsinhibitTh1-primingcapacityofpDCfollowingCpGstimulationpDC48hCpGCFACS-sortedpDCAllogenicCD4+naïveT6daysPMA/IonomycinICSpDC+BsubsetpDC10+5hi5+5-IFN-gCD43CD27CD9CD44CD10+CD5hiCD5+CD5-ILT3SurfacemarkersofneonatalBsubsetsStudyofBcellreplicationhistoryAdultBcellsNeonatalBcellsInnateBregStudyofBcellVDJrepertoireandCDR3lengthCD5hiBregshaveaJH4D6preferenceCD10+CD5hiBregsshowan...
