B细胞激活1.ppt

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1、B细胞激活BCellActivationB细胞抗原识别受体与信号转导T-B细胞相互作用与B细胞的增殖分化B细胞的增殖与分化B细胞对T细胞非依赖抗原的应答B细胞抗原识别受体与信号转导1chapternineBCellActivationT细胞抗原识别信号的转导pathwayApathwayBpathwayCPKCcalcineurinMAPkinasePIP2DAG+IP3Ras-GDPRas-GTPCa2+RafPLC-SosNF-ATOCTNF-BAP-1NF-ATOCTPKCGrb-2I-BNF-BNF-BNF-ATNF-AT-pc-Junc-FosAKTB

2、7CD28PI3-KLATSLP-76ZAP-70Peptide-MHCTCRLckFynCD45CD4PTPdomainsY505pITAMITAMYpYpNUCLEUSCELLMEMBRANEIL-2geneYpYpYpGSK3GadsNCK细胞骨架重排免疫突触PIPIP3BCRIg/IgITAM受体交联（形成免疫突触）偶联PTK活化（Lyn、Fyn、Blk）ITAM磷酸化（活化）招募胞浆PTK（Syk）PTK磷酸化（活化）衔接蛋白（BLNK、SLP-65）PLC-PIP2DAG+IP3激活PKC活化钙调磷酸酶活化MAP激酶级联反应活化转录因子（NF-

3、B、NFAT、AP-1）与特异性基因的启动子结合，启动基因转录转位GEF（Vav）CD81(TAPA-1)CD19YAgC3dgCD21(CR2)Ig/IgBCRTCRMHCCD4BlkZAP-70LckFynLynSykpeptideAPCTcellBcellAcomparisonofantigen-recognitionstructuresandtherelatedmoleculesinTcellandBcellmaincomponentTcellBcellMembraneantigenreceptorTCRBCRmoleculeITAM-bearin

4、gmoleculeCD3,,,Ig,Igco-receptorCD4orCD8CD21,CD19,CD81PTPCD45CD45PTKSrcfamilyLck,FynLyn,Fyn,Blk,LckSykfamilyZAP-70SykMAPK-relatedinitiationadaptorLAT,SLP-76BLNK,SLP-65pathwaysmallGproteinRas(Rac)Rac(Ras)GEFSosVavMAPkinaseErkJnkSecondsignalreceptorCD28CD40ligandB7CD40LPTK:proteintyrosi

5、nekinase;PTP:proteintyrosinephosphatase;MAP:mitogen-activatedprotein;GEF:guaninenucleotideexchangefactor;LAT:linkerforactivationofTcell;BLNK:Bcelllinkerprotein;ZAP:zetachain-associatedprotein;ITAM:immunoreceptortyrosine-basedactivationmotifAcomparisonofmaincomponentsinsignaltransductionfor

6、TandBcellsErk-andJnk-pathwaysinMAPkinase-relatedsignalingcascade?PakRafMekkMekLnkkErkJnkFosJunAP-1RasRac,cdc42TactivationBactivation/StressGTPproteinMAPKKKKMAPKKKMAPKKMAPKTranscriptionfactorp38T-B细胞相互作用与B细胞的增殖分化chapternineBCellActivation2BCRhaptencarrierTH2CkCk-RCD40LCD40lysosomeIichainMHC

7、classIIAbT、B淋巴细胞分别识别载体和半抗原，通过相互作用诱导抗体产生Agsignal1Bcellendoplasmicreticulumsignal2①BTH2CD40LCD40CD28B7Ck(e.g.IL-4)BCRIg-IgAg①①②②CollaborationbetweenTcellandBcellSecondsignalsforBcellactivation:ligatedCD40andCkreceptorAbMTOC:microtubule-organizingcenterWhenanac