Mechanisms of Lymphocyte Activation and Immune Regulation XI: B Cell Biology PDF
Preview Mechanisms of Lymphocyte Activation and Immune Regulation XI: B Cell Biology
Mechanisms of Lymphocyte Activation and Immune Regulation XI Advances in Experimental Medicine and Biology EDITORIALBOARD:NATHANBACK,StateUniversityofNewYorkatBuffalo IRUNR.COHEN,TheWeizmannInstituteofScience DAVIDKRITCHEVSKY,WistarInstitute ABELLAJTHA,N.S.KlineInstituteforPsychiatricResearch RODOLFOPAOLETTI,UniversityofMilan RecentVolumesinthisSeries Volume588 HYPOXIAANDEXERCISE EditedbyRobertC.Roach,PeterD.Wagner,andPeterH.Hackett Volume589 NEURALCRESTINDUCTIONANDDIFFERENTIATION EditedbyJean-PierreSaint-Jeannet Volume590 CROSSROADSBETWEENINNATEANDADAPTIVEIMMUNITY EditedbyPeterD.Katsikis,BaliPulendranandStephenP.Schoenberger Volume591 SOMATICCELLNUCLEARTRANSFER EditedbyPeterSutovsky Volume592 REGULATORYMECHANISMSOFSTRIATEDMUSCLECONTRACTION EditedbySetsuroEbashiandIwaoOhtsuki Volume593 MICROARRAYTECHNOLOGYANDCANCERGENEPROFILING EditedbySimoneMocellin Volume594 MOLECULARASPECTSOFTHESTRESSRESPONSE EditedbyPeterCsermelyandLaszloVigh Volume595 THEMOLECULARTARGETSANDTHERAPEUTICUSESOFCURCUMIN INHEALTHANDDISEASE EditedbyBharatB.Aggarwal,Yung-JoonSurhandShishirShishodia Volume596 MECHANISMSOFLYMPHOCYTEACTIVATIONANDIMMUNEREGULATIONXI EditedbySudhirGupta,FrederickAlt,MaxCooper,FritzMelchers andKlausRajewsky AContinuationOrderPlanisavailableforthisseries.Acontinuationorderwill bring delivery of each new volume immediately upon publication. 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Mechanisms of Lymphocyte Activation and Immune Regulation XI B Cell Biology Edited by SUDHIR GUPTA University of California Irvine Irvine, California FREDERICK ALT Harvard Medical School Boston, Massachusetts MAX COOPER University of Alabama Birmingham, Alabama FRITZ MELCHERS University of Basel Basel, Switzerland KLAUS RAJEWSKY Harvard Medical School Boston, Massachusetts Editors: SudhirGupta FritzMelchers SchoolofMedicine BiozentrumAbt.Zellbiologie CollegeofHealthSciences MaxPlanckInstituteforInfectionBiology UniversityofCalifornia Berlin,4056 Irvine,CA92697 Germany USA [email protected] [email protected] [email protected] FrederickW.Alt KlausRajewsky DepartmentofGenetics CenterforBloodResearch Children’sHospitalBoston HarvardMedicalSchool Boston,MA02115 Boston,MA02115 USA USA [email protected] [email protected] MaxD.Cooper Inst.Medical/TumorResearchLaboratories UniversityofAlabama Birmingham,AL35294 USA [email protected] LibraryofCongressControlNumber:2006933718 Proceedingsfromthe11thInternationalConferenceonBcellBiologyheldinNewportBeach,CA, February3–5,2006. ISBN-10:0-387-46527-8 e-ISBN-10:0-387-46530-8 ISBN-13:978-0-387-46527-2 e-ISBN-13:978-0-387-46530-2 Printedonacid-freepaper. ©2007SpringerScience+BusinessMedia,LLC All rights reserved. This work may not be translated or copied in whole or in part without the written permission of the publisher (Springer Science+Business Media, LLC, 233 Spring Street, New York, NY 10013, USA), except for brief excerpts in connection with reviews or scholarly analysis.Useinconnectionwithanyformofinformationstorageandretrieval,electronicadaptation, computersoftware,orbysimilarordissimilarmethodologynowknownorhereafterdevelopedis forbidden. The use in this publication of trade names, trademarks, service marks, and similar terms, even if theyarenotidentifiedassuch,isnottobetakenasanexpressionofopinionastowhetherornot theyaresubjecttoproprietaryrights. 10 9 8 7 6 5 4 3 2 1 springer.com Contents Preface.......................................................................................... vii ListofContributingSpeakers.................................................................... ix BCellDevelopmentandImmunoglobulinGeneRearrangement 1. RegulationandFunctionoftheE2AProteinsinBCellDevelopment.................... 1 CornelisMurre 2. MultipleRolesforBlimp-1inBandTLymphocytes..................................... 9 DavidSavitsky,LuisaCimmino,TracyKuo,GislaˆineA.Martins andKathrynCalame 3. MemoryBCellEvolution:BCellBiology................................................ 31 LouiseJ.McHeyzer-WilliamsandMichaelG.McHeyzer-Williams 4. BCR-linkedFactorsinDevelopmentalFateDecisions................................... 47 RandallJ.BrezskiandJohnG.Monroe 5. GeneRegulatoryNetworksthatOrchestratetheDevelopmentofBLymphocyte Precursors................................................................................ 57 HarinderSingh,JaganM.R.PongubalaandKayL.Medina 6. RulesfortheRearrangementEventsattheLChainGeneLocioftheMouse............ 63 FritzMelchers,TamotsuYamagami,AntoniusRolink andJanAndersson 7. RegulationofAIDFunctionInVivo...................................................... 71 ReikoShinkura,Il-miOkazaki,TaroMuto,Nasim A.BegumandTasukuHonjo 8. TargetingofAIDtoImmunoglobulinGenes.............................................. 83 UrsulaStorb,HongMingShen,SimonneLongerich,Sarayu Ratnam,AtsushiTanaka,GrazynaBozekandSerhiyPylawka 9. TargetingAIDtotheIgGenes........................................................... 93 ZiqiangLi,ZhonghuiLuo,DianaRonai,FeiLiKuang, JonathanU.Peled,MariaD.Iglesias-UsselandMatthewD.Scharff 10. DNAReplicationtoAidSomaticHypermutation.........................................111 ZhenmingXu,HongZan,ZsuzsannaPalandPaoloCasali BCellSignallingReceptonEditingToleranceandAutoimmunity 11. RegulationofActivationInducedDeaminaseviaPhosphorylation.......................129 UttiyaBasu,JayantaChaudhuri,RyanT.Phan,Abhishek DattaandFrederickW.Alt 12. ModulationofMHCClassIISignalTransductionbyCD19.............................139 v vi Contents DavidM.Mills,JohnC.StolpaandJohnC.Cambier 13. RoleofNF(cid:2)BSignalinginNormalandMalignantBCellDevelopment.................149 YoshiteruSasaki,MarcSchmidt-Supprian,Emmanuel Derudder,KlausRajewsky 14. FcReceptor–likeProteins(FCRL):ImmunomodulatorsofBCellFunction..............155 GötzR.A.Ehrhardt,Chuen-MiinLeu,ShuangyinZhang, GüzideAksu,TanishaJackson,ChrisHaga,JoyceT.Hsu, DanielSchreeder,RandallS.DavisandMaxD.Cooper 15. ToleranceMechanismsintheLatePhaseoftheAntibodyResponse.....................163 ChristopherC.Goodnow,JamesA.Campbell,LixinRui andCarolaG.Vinuesa 16. RoleofRS/(cid:2)DEinBCellReceptorEditing..............................................169 JoséLuisVelaandDavidNemazee 17. TheRegulationofReceptorEditing......................................................173 MarkS.Schlissel 18. BCellHyporesponsivenessandAutoimmunity:ANewParadigm........................181 ChristineGrimaldi,EmilNashi,JeganathanVenkatesh andBettyDiamond Index.............................................................................................191 Preface Inrecentyears,majordevelopmentshavebeenmadeinunderstandingvariousgeneticandepigenetic regulatory processes that are critical for the generation of B cell repertoires. These include the role of chromatin regulation and nuclear organization in understating the IgH gene regulation. A roleandmechanismofDNArepairproteinsinsomatichypermutationhasbeenelucidated.Genetic mutationstudieshavebeeninstrumentalinprovidinginsightintosomeofthemechanismsinvolved intargetingCSRtovariousswitchDNAregionslocatedupstreamofCregiongenes,especiallyarole ofAIDmotifs,transcriptionandR-loops.Recentstudiessupportadominantroleofreceptorediting in central B cell tolerance and signaling pathways that regulate receptor editing in self-reactive and non-self-reactive immature B cells. These were some of the topics of discussion at the 11th International Conference on B cell Biology. These proceedings highlight recent developments in lymphocytedevelopment,Iggenerearrangementsandsomatichypermutation,chromatinstructure modification,Blymphocytesignalingandfate,receptoreditingandautoimmunity. FirstsectiondealswiththemechanismsofBcelldevelopmentandimmunoglobulingenearrange- ments. A contribution of E2A-protein in the induction of B cell lineage specific gene expression programandtheinductionofclassswitchrecombinationarediscussed.Blimp-1regulatesanumber oftranscriptionfactorsandinfluencesmultiplegeneexpressionprogramsMultiplerolesofBlimp-1 inthedevelopmentanddifferentiationofcellsofBcelllineagearepresented.Also,moreinterest- ingly,recentdataoftheroleofBlimp-1inthymocytedevelopment,peripheralTcellhomeostasis inresponsesofTcellstoTCRarepresented.NovelmechanismsofclonalselectioninThcelland BcellcompartmentsofregulationofmemoryBcellresponses,aswellastheroleofBCR-linked factors in developmental fate decisions are reviewed. Several speakers presented interesting and novel data for regulation of AID functions in SHM and CSR, including chromatin modification, cis-actingsequencesandphosphorylationofAID. Second section includes presentation regarding BCR signaling, receptor editing, immunological tolerance and autoimmunity. It has been demonstrated that CD19 associates with MHC class II signaling complex in B cells, and is required for optimal MHC class II-mediated downstream signaling. Two alternative pathways of NF-(cid:2)B have emerged in normal and malignant B cell activationanddevelopmentbyBCRandBAFF-R.AselectiveexpressionofFcR-likeproteinsduring differentphasesofBcelldevelopmentmakestheminterestingBcelldifferentiationmarkers.Since theseproteins,byvirtueofcytoplasmicITIMand/orITAMsequences,displayimmunoregulatory activities, they are interesting therapeutic targets for disorders of B cells. A central role of ERK signaling pathway in integrating opposing signals to regulate the induction of Blimp and plasma cell differentiation is reviewed. Receptor editing is one of the mechanisms by which autoreactive B cells can undergo tolerance. A significant progress has been made in understanding mecha- nismswhichregulatereceptorediting,includingaroleoftherecombiningsequences(RS)andits humanhomologuethekappadeletingelement((cid:2)DE)inBCRediting.RegulationofRAGgenesin immatureself-reactiveandself-tolerantBcells,receptoreditingofIgHC,andenforcementofallelic exclusioninthesettingofreceptoreditingarereviewed.Anewparadigmthathyporesponsiveness of B cells constitutes a critical component of a genetic diathesis to autoimmunity may represent environmentally-inducedpredispositiontoautoimmunity. This volume should be of interest to immunologists, cell biologists, academic clinicians, and scientists. SudhirGupta vii viii Preface FrederickAlt MaxCooper FritzMelchers KlausRajewsky List of Contributing Speakers FrederickAlt TheHowardHughesMedicalInstitute,TheChildren’sHospital,HarvardMedical School,Boston,MA02115. KathrynCalame DepartmentofMicrobiology,ColumbiaUniversityCollegeofPhysiciansand Surgeons,NewYork,NY10032 JohnC.Cambier IntegratedDepartmentofImmunology,NationalJewishMedicalandResearch Center,UniversityofColoradoHealthScienceCenter,Denver,CO80206 PaoloCasali CenterforImmunology,UniversityofCalifornia,Irvine,CA92697 MaxD.Cooper HowardHughesInstitute,UniversityofBirmingham,AL33294-2182 BettyDiamond DepartmentofMedicine,ColumbiaUniversity,NewYork,NY10032 Christopher Goodnow John Curtin School of Medical Research, The Australian National University,MillsRoad,Canberra,ACTAustralia0200 TasukuHonjo DepartmentofImmunologyandGenomicMedicine,KyotoUniversityGraduate SchoolofMedicine,Kyoto,Japan606-8501 MichaelG.McHeyzer-Williams ScrippsResearchInstitute,LaJolla,CA92093 FritzMelchers DepartmentofCellBiology,Biozentrum,UniversityofBasel,Basel,Switzerland JohnG.Monroe UniversityofPennsylvania,Philadelphia,PA19128 CornelisMurre UniversityofCaliforniaatSanDiego,LaJolla,CA92093 DavidNemazee DepartmentofImmunology,TheScrippsResearchInstitute,LaJolla,CA92037 KlausRajewsky TheCBRInstituteforBiomedicalResearch,HarvardMedicalSchool,Boston, MA02115 MarkS.Schlissel UniversityofCaliforniaatBerkeley,Berkeley,CA94720 Matthew D. Scharff Departments of Cell Biology and Medicine, Albert Einstein College of Medicine,Bronx,NY10461 Harinder Singh Department of Molecular Genetics and Cell Biology, University of Chicago, Chicago,IL60637 Ursula Storb Department of Molecular Genetics and Cell Biology, University of Chicago, IL 60637 ix 1 Regulation and Function of the E2A Proteins in B Cell Development Cornelis Murre∗ 1.1. Introduction E-proteins belong to a family of transcriptional regulators, helix-loop-helix proteins (HLH), which regulate multiple developmental pathways in verte- brate organisms. Throughout B cell development, E-proteins play critical roles. MembersoftheE-proteinfamilyincludetheE2AproteinsE12andE47aswell astwocloselyrelatedgeneproducts,E2-2andHEB.TheE2A-proteinscontribute to B cell commitment, to induce a B lineage specific gene expression program, to activate antigen receptor gene rearrangement, to induce class switch recom- bination and to promote developmental progression. Here, I present the current status on the function and regulation of E2A proteins in B cell development. 1.2. E2A proteins The helix-loop-helix proteins can be divided into distinct categories based on expression patterns and biochemical properties1. Class I bHLH proteins, also named E-proteins, are DNA binding proteins that recognize specific DNA sequences(E2-boxsite)2.E-proteinsareexpressedinmanydifferenttissuesbut their levels of expression differ significantly among lineages and tissues. In lymphoid cells they bind DNA either as homo- or as heterodimers with other E-proteins. Four E-proteins are expressed in lymphoid cells, named E12, E47, E2-2 and HEB3. E-proteins contain an HLH dimerization domain and a basic region that mediates DNA binding4,4a. In addition, two conserved stretches of amino acids are present in E-proteins that function as either transactivation or repressordomains.ThetwodomainsarenamedtheAD1andAD2domains5,6,7. ∗CornelisMurre,UniversityofCalifornia,SanDiego,9500GilmanDrive,0377,LaJolla, CA92093 1
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