B-cell tolerance-

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1、B-celltolerance:mechanismsandimplicationsContents1.Introduction2.Decisionbetweentoleranceandimmunity3.Mechanismsoftolerance4.BreakdownofB-celltolerance☆CompanyLogoIntroductionItisessentialthattolerancebeimposedontheB-cellaswellastheT-cellrepertoires.Themainreasonsforthisare:(a)thespectr

2、umoffunctionalactivitiesperformedbyB-cellsthatincludenotonlyantibodyproduction,butalsoantigenpresentationandsecretionofpro-inflammatoryandanti-inflammatorycytokines;(b)thefactthattheB-cellrepertoireisgeneratedintwostages:inthefirst,V(D)Jrecombinationoccurswithinthebonemarrow(BM)tocreate

3、the‘pre-immunerepertoire’,whilethesecondinvolvessomatichypermutation(SMH)ofimmunoglobulin(Ig)variableregiongeneswithingerminalcentres(GCs)followingantigenstimulationandprovisionofco-stimulatorysignalsfromT-cellsand/orexternalpathogensCompanyLogoIntroductionIneachcase,theprimarygoalistod

4、iversifytherepertoireofB-cellspecificitiesagainstforeignantigens,althoughtherandomnatureofbothV(D)JrecombinationandSMHinevitablyleadstotheappearanceofcellsexpressinganti-selfB-cellreceptors(BCR)withinbothrepertoires.toleranceCompanyLogoIntroductionMultipleoverlappingmechanismsoftoleranc

5、eatseveralcheckpointsinB-celldifferentiationhaveevolvedtodealwiththeever-presentthreatofautoimmunityposedbythegenerationofselfreactiveB-cells.CompanyLogoDecisionbetweentoleranceandimmunityForB-cells,thedecisionbetweentoleranceandimmunitycanstillbeexplainedwithintheframeworkofthetwo-sign

6、alhypothesisofBretscherandCohn.CompanyLogoDecisionbetweentoleranceandimmunityCompanyLogoDecisionbetweentoleranceandimmunitypotentialrolefortargettissuefactorsininfluencingthedecisionbetweentoleranceandimmunityrequiresemphasisDecisionbetweentoleranceandimmunityAnothermechanismcontributin

7、gtothedecisionbetweentoleranceandimmunityworthhighlightinghereistheallegedcapacityofB-cellsthemselvestoactasregulatorsratherthaneffectors..CompanyLogoMechanismsoftoleranceTherequirementformultiplecheckpointstopurgetheB-cellrepertoireofunwantedanti-self-specificitiesisnowwellacc