浙江大学医学免疫学经典课件免疫9、13-B细胞VIP免费

LieWang(汪洌）浙江省杭州市浙江大学紫金港校区医学院科研楼A810-814医学院免疫学研究所BlymphocytesandHumoralImmuneResponseThediscoveryofBcellimmunity1954-BruceGlick,OhioStateUniversityStudiesonthefunctionofthebursaofFabricius,alymphoidorganinthecloacalregionofthechickenBursawaslaterfoundtobetheorganinwhichantibodyproducingcellsdeveloped–antibodyproducingcellswerethereaftercalledBcellsMammalsdonothaveabursaofFabriciusTransfermarkedfoetallivercellsOriginofBcellsandorganofBcellmaturationNoMatureBcellsAfterbirth,developmentcontinuesinthebonemarrowNormalbonemarrowDefectivebonemarrowMaturemarkedBcellsinperipheryBcelldevelopmentstartsinthefoetalliverBcelldevelopmentinthebonemarrowBRegulatesconstructionofanantigenreceptorBoneMarrowprovidesaMATURATION&DIFFERENTIATIONMICROENVIRONMENTforBcelldevelopmentEnsureseachcellhasonlyonespecificityBChecksanddisposesofself-reactiveBcellsBExportsusefulcellstotheperipheryBProvidesasiteforantibodyproductionBSecretedFactors-CYTOKINES2.SecretionofcytokinesbystromalcellsBBonemarrowstromalcellsnurturedevelopingBcellsTypesofcytokinesandcell-cellcontactsneededateachstageofdifferentiationaredifferentStromalcell1.Specificcell-cellcontactsbetweenstromalcellsanddevelopingBcellsCell-cellcontactBonemarrowstromalcellMaturingBcellsBBStromalcellBlineagecommitmentHSC(hematopoieticstemcell)MPP(淋巴系髓系多能前体细胞)ELP(earliestlymphocyteprogenitor)ETP(earlyT-lineageprogenitor)CLP(commonlymphoidprogenitor)HSCHSCDevelopmentandmigrationofBcells(Anoverview)StagesofdifferentiationinthebonemarrowaredefinedbyIggenerearrangementBCELLSTAGEIgHGENECONFIGURATIONStemcellEarlypro-BLatepro-BLargepre-BGermlineDHtoJHVHtoDHJHVHDHJHPre-BcellreceptorexpressedIglightchaingenehasnotyetrearrangedBcellreceptorTransientlyexpressedwhenVHDHJHCHisproductivelyrearrangedIg&IgsignaltransductionmoleculesCHHeavychainVHDHJHLightchainVLJLCLVpreB5Pre-Bcelldevelopmentiscoupledwithrearrangementofheavy-chainBcelldevelopmentiscoupledwithrearrangementofheavy-chainBcelldevelopmentiscoupledwithrearrangementofheavy-chainBcelldevelopmentiscoupledwithrearrangementofheavy-chainBcelldevelopmentiscoupledwithrearrangementofheavy-chainBcelldevelopmentiscoupledwithrearrangementofheavy-chainSplicingofIgMandIgDRNAC1C2C3C4C1C2C3pA1VDJC1C2C3C4C1C2C3VDJAAARNAcleavedandpolyadenylatedatpA2VDJCIgMmRNAVDJCIgDmRNAC1C3CCVDJC1C2C3C4C1C2C3DNApA1pA2VDJTwotypesofmRNAcanbemadesimultaneouslyinthecellbydifferentialusageofalternativepolyadenylationsitesandsplicingoftheRNARNAcleavedandpolyadenylatedatpA1AAABcelldevelopmentiscoupledwithrearrangementofheavy-chain6000heavychainscombinedwith320lightchains1.9X106AbsLigationofthepre-Bcellreceptor1.EnsuresonlyonespecifictyofAbexpressedpercellLargePre-BStromalcellUnconfirmedligandofpre-Bcellreceptor2.TriggersentryintocellcycleALLELICEXCLUSIONExpressionofageneononechromosomepreventsexpressionofthealleleonthesecondchromosome1.SuppressesfurtherHchainrearrangement2.Expandsonlythepre-BcellswithinframeVHDHJHjoinsEvidenceforallelicexclusionAllotypescanbeidentifiedbystainingBcellsurfaceIgwithantibodiesa/ab/ba/bYBbYBaYBbYYBabYBaANDALLOTYPE-polymorphismintheCregionofIg–oneallotypeinheritedfromeachparentSuppressionofHchainrearrangementbypre-Bcellreceptorpreventsexpressionoftwospecificitiesofantibodypercell(ReferbacktoDreyer&Bennethypothes...