B淋巴细胞刺激因子-BLyS-研究进展

B(BLyS)吴一凡　张双全＊(,210097)　B(BLyS)1999,(TNF)..B(IgM);B.BLyS.BLyS、、.　B(BLyS),,,,　Q7　　B(Blymphocytestimulator,BLyS),TALL-1(TNF-andApoL-relatedleukocyteexpressedligand1)、BAFF(BcellactivatingfactorbelongingtotheTNFfamily)、THANK(TNFhomologuethatactivatesapoptosis、NF-κBandJNK),(TNF),Shu[1]1999,[2～4].BLyS,T.BLySB,Anti-IgMIL-4B,;.BLyS,(germinalcenterGC)BIgM,[5].1　BLyS　　BLyS28531.3ku,(N242),,93%.BLyS13q32-34,mRNA2.6kb[3].BLyS,.BLySTNF,Ⅱ,L47～Q73;(CA134～L285)(),(sBLyS)[6];N.TNF,:APRIL28.7%,TNF-α16.2%,FasL16%,LIGHT15%,LT-α14.1%[3,4](1).BLyS,8β,α,.Fig.1　DendrogramsofTNFsuperfamilyligands[3]1　TNF[3]　　Moore[2]Schneider[3]RNABLySmRNA、、,、、　＊.　Tel:[phone],E-mail:[e-mail]　:2000-12-19,:2001-02-23·658·　　Prog.Biochem.Biophys.　　　　　2001;28(5)、.,,IFN-γ,T.BLySmRNAK562、HL-60、THP-1U937,BT(Raji、RPMI1788、MOLT4、Jurkat).2　BLyS2.1　B　　BLySB,,BLySB,CD40LB.,B,Anti-IgM,BLyS,IgMIgA,BLyS[3].,BLySBIgM;;(GC)[7].Moore[2]BLyS(sBLyS),B220+,B,IgAIgM,IgG[2].,BLySB,FasL-Fas[5];BLyS(RajiCOS7),BLyS[8].2.2　T　　BLySB,T.Gross[9],BLyS,T,CD4+CD8+T;CD44,LECAM-1,,BLyST(B5%)[10],TBLySTACI.BLyST.　　:BLyS,CD40L,BLySTB[8],B,IgM;B,.3　BLyS　　,BLyS,.Schneider[3]BLyS-,,BLySCD19+B;BLySB,T、.　　TNF“”:B(Bcellmaturationprotein,BCMA)CAML(transmembraneactivatorandCAML-interactor,TACI)BLyS[7,9～13].　　BCMA185,BCMAB,Ⅰ,N6.BCMA.BCMA16p13,mRNA1.2kb.HEK293TBCMABLyS:B,BCMABLySB,BLySB[12,13].　　TACI293Ⅲ,,54%.(calcium-modulatorandcyclophilinligand,CAML)NF-AT[14].BT,(S33～C66C70～C104).BCMA,TNF.TACImRNA1.4kb,、、.RajiTACI,BLyS.TACIBLySB[9～11].·659·2001;28(5)　　　　　　Prog.Biochem.Biophys.　　BLySB,Labbi[5]:TNF,BLySBCMATACI“”(BLyS-BCMATRAF5、TRAF6、NIKIKKsNF-κB[12];BLyS-TACITRAF2、TRAF5、TRAF6NF-κB、JNKNF-AT[10]),Bcl-2,Bim,B(BCR)/TNFRFas,.BLySU937caspase-3[4],BLyS.4　BLyS　　BLyS(SLE)[9,15,16]:、Peyerspatch,B220+;IgM、IgE、IgAIgG;;;T,.BLyS.BLySBCRB,Bcl-2[5].sBLySB,BLyS.　　BLyS97%,,BLyS.Gross[9]Thompson[13]BLySTACIBCMA,IgG1FcsTACI-FcsBCMA-Fc,“”(decoyreceptor)BLyS,BLySBLySB.TNFR2-Fc.,BLySB.,BLySSLE,BLyS.　　BLyS,,:BLyS,.BLyS,(HGSI、Genentech、Amgen、ZymoGenetics)BLyS,HGSIBLySFDA,Ⅰ,(CVID).　　　1　ShuHB,HuW,JohnsonH.TALL-1isanovelmemberoftheTNFfamilythatisdown-regulatedbymitogens.JLeukocBiol,1999,65(5):680～6832　MoorePA,BelvedereO,OrrA,etal.BLyS:MemberofthetumornecrosisfactorfamilyandBlymphocytestimulator.Science,1999,285(5425):260～2633　SchneiderP,MackayF,SteinerV,etal.BAFF,anovelligandofthetumornecrosisfactorfamily,stimulatesBcellgrowth.JExpMed,1999,189(11):1747～17564　MukhopadhyayA,NiJ,ZhaiY,etal.Identificationandcharacterizationofanovelcytokine,THANK,aTNFhomologuethatactivatesapoptosis,nuclearfactor-κB,andc-JunNH2-terminalkinase.JBiolChem,1999,274(23):15978～159815　LabbiY,StrasserA.Lymphocytesurvival-IgnoranceisBLyS.Science,2000,289(5481):883～8846　NardelliB,BelvedereO,RoschkeV,etal.SynthesisandreleaseofB-lymphocytestimulatorfrommyeloidcells.Blood,2001,97(1):198～2047　YanM,MarstersSA,GrewalIS,etal.IdentificationofareceptorforBLySdemonstratesacrucialroleinhumoralimmunity.NatureImmunology,2000,1(1):37～418　DoRK,HatadaE,LeeH,etal.AttenuationofapoptosisunderliesBlymphocytestimulatorenhancementofhumoralimmuneresponse.JExpMed,2000,192(7):953～9649　GrossJA,JohnstonJ,MudriS,etal.TACIandBCMAarereceptorsforaTNFhomologueimplicatedinB-cellautoimmunedisease.Nature,2000,404(6781):995～99910WuY,bressetteD,CarrellJA,etal.Tumornecrosisfactor(TNF)receptorsuperfamilymemberTACIisahighaffinityreceptorforTNFfamilymembersAPRILandBLyS.JBiolChem,2000,275(45):35478～3548511XiaXZ,TreanorJ,SenaldiG,etal.TACIisaTRAF-interactingreceptorforTALL-1,atumornecrosisfactorfamilymemberinvolvedinBcellregulation.JExpMed,2000,192(1):134～14312ShuHB,JohnsonH.BcellmaturationproteinisareceptorforthetumornecrosisfactorfamilymemberTALL-1.ProcNatlAcadSciUSA,2000,97(16):9156～916113ThompsonJS,SchneiderP,KalledSL,etal.BAFFbindstothetumornecrosisfactorreceptor-likemoleculeBcellmaturationantigenandisimportantformaintainingtheperipheralBcellpopulation.JExpMed,2000,192(1):129～135·660·　　Prog.Biochem.Biophys.　　　　　2001;28(5)14vonBulowGU,BramRJ.NF-ATactivationinducedbyaCAML-interactingmemberofthetumornecrosisfactorreceptorsuperfamily.Science,1997,278(5335):138～14115KhareSD,SarosiI,XiaXZ,etal.SevereBcellhyperplasiaandautoimmunediseaseinTALL-1transgenicmice.ProcNatlAcadSciUSA,2000,97(16):3370～337516MackayF,WoodcockSA,LawtonP,etal.MicetransgenicforBAFFdeveloplymphocyticdisordersalongwithautoimmunemanifestations.JExpMed,1999,190(11):1697～1710ProgressonBLymphocyteStimulator(BLyS)WUYi-Fan,ZHANGShuang-Quan＊(LaboratoryofBiochemistryandMolecularBiology,NanjingNormalUniversity,Nanjing210097,China)Abstract　Blymphocytestimulator(BLyS)isarecentlyidentifiedmemberofthetumornecrosisfactor(TNF)superfamilythatcostimulatesBlymphocyteproliferationanddifferentiation.ItprominentlyenhancesthehumoralresponsestobothTcell-independentandTcell-dependentantigens.BLySisrequiredtosustainproliferationofsplenicgerminalcenter(GC)Bcellinvivo.Asanantiapoptoticcytokine,BLySprovidessurvivalsignalsbyinducingup-regulationofBcl-2.TransgenicmiceoverexpressingBLySinlymphoidcellsdevelopssymptomscharacteristicofsystemiclupuser