《医学免疫学》10 抗体 陆青-教学课件（非AI生成）.ppt

*ThecharacteristicYshapeofIgGisattributedtothedifferentdomains:theFabdomains(twodomainsperIgGmolecule)andtheFcdomain,whicharelinkedbythehingeregion.作用部位*toxoids,lacktoxicactivitybutretainthereceptor-bindingsite.*****CD16不能结合循环中的单体IgG*********编码基因重排，形成由不同基因节段组成的功能基因1010*asonlyBcellsthatexpressapre-BCRarepositivelyselectedandabletomaturefurther.*Fig.3.PI3KregulatesIgLgenerecombination.(A)Expressionofasignaling-competentpre-B-cellantigenreceptor(pre-BCR)onthecellsurfaceinducesthephosphoinositide3-kinase(PI3K)pathwaythroughautonomoussignalingthatismediatedbySyk(spleentyrosinekinase).PI3KactivatesproteinkinaseB(PKBorAKT)thatphosphorylatesforkheadboxO(FOXO)transcriptionfactors,thusleadingtotheirproteasomaldegradation.Undertheseconditions,therecombination-activatinggene(RAG)proteinsaretranscribedatverylowlevels,andtherefore,recombinationprocessesattheimmunoglobulinlightchain(IgL)genesaresuppressed.DuetotheinactivationofFOXOs,pre-BCRexpressingcellsareprimedforproliferation.(B)However,pre-BCR-mediatedactivationofSH2-domain-containingleukocyteproteinof65kDa(SLP-65)inhibitsPI3Kactivity.FOXOtranscriptionfactorsarethereforereleasedfromAKT-mediatednegativeregulationandabletoinducetheexpressionoftheirtargetgenes.ActiveFOXOspromoteexitofthecellcycleandinduceexpressionoftheRAGproteins.AsaconsequenceofenhancedRAGexpression,recombinationoftheIgLgenesisinitiated.Thus,inthecompleteabsenceofSyk-mediatedsignals,VDJrecombinationisconstitutivelyactivewithoutadditionaltriggering.Supportingthis,Syk?ZAP-70doubledeficientpre-BcellsshowlossofallelicexclusionanduncontrolledVDJrecombinationofthe?HClocus(105).InSLP-65-deficientmice,incontrast,IgLchaingenerecombinationisimpaired,whichleadstocompromisedr