IgE Antibodies: Generation and Function PDF
Preview IgE Antibodies: Generation and Function
Current Topics in Microbiology and Immunology Juan J. Lafaille Maria A. Curotto de Lafaille E ditors IgE Antibodies: Generation and Function Current Topics in Microbiology and Immunology Volume 388 Serieseditors RafiAhmed SchoolofMedicine,RollinsResearchCenter,EmoryUniversity,RoomG211,1510CliftonRoad,Atlanta,GA30322, USA KlausAktories MedizinischeFakultät,InstitutfürExperimentelleundKlinischePharmakologieundToxikologie,Abt.I, Albert-Ludwigs-UniversitätFreiburg,Albertstr.25,79104Freiburg,Germany RichardW.Compans DepartmentofMicrobiologyandImmunology,EmoryUniversity,1518CliftonRoad,CNR5005,Atlanta,GA30322, USA MaxD.Cooper DepartmentofPathologyandLaboratoryMedicine,GeorgiaResearchAlliance,EmoryUniversity,1462Clifton Road,Atlanta,GA30322,USA JorgeE.Galan BoyerCtr.forMolecularMedicine,SchoolofMedicine,YaleUniversitym,295CongressAvenue,room343, NewHaven,CT06536-0812,USA YuriY.Gleba ICONGeneticsAG,BiozentrumHalle,Weinbergweg22,06120Halle,Germany TasukuHonjo FacultyofMedicine,DepartmentofMedicalChemistry,KyotoUniversity,Sakyo-ku,YoshidaKyoto606-8501,Japan YoshihiroKawaoka InfluenzaResearchInstitute,UniversityofWisconsin-Madison,575ScienceDrive,Madison,WI53711,USA BernardMalissen Centred’ImmunologiedeMarseille-Luminy,ParcScientifiquedeLuminy,Case906,13288,MarseilleCedex9, France MichaelB.A.Oldstone DepartmentofImmunologyandMicrobialScience,TheScrippsResearchInstitute,10550NorthTorreyPinesRoad, LaJolla,CA92037,USA RinoRappuoli NovartisVaccines,ViaFiorentina1,Siena53100,Italy PeterK.Vogt DepartmentofMolecularandExperimentalMedicine,TheScrippsResearchInstitute,10550NorthTorreyPines Road,BCC-239,LaJolla,CA92037,USA HonoraryEditor:HilaryKoprowski(deceased) FormerlyatBiotechnologyFoundation,Inc.,Ardmore,PA,USA More information about this series at http://www.springer.com/series/82 Juan J. Lafaille Maria A. Curotto de Lafaille (cid:129) Editors IgE Antibodies: Generation and Function Responsible Series Editor: Tasuku Honjo 123 Editors Juan J.Lafaille Maria A.Curottode Lafaille SkirballInstituteand Department SingaporeImmunologyNetwork (SIgN) ofPathology AgencyforScience, Technologyand New YorkUniversitySchool ofMedicine Research New York Singapore USA Singapore ISSN 0070-217X ISSN 2196-9965 (electronic) Current TopicsinMicrobiology andImmunology ISBN 978-3-319-13724-7 ISBN 978-3-319-13725-4 (eBook) DOI 10.1007/978-3-319-13725-4 LibraryofCongressControlNumber:2014956362 SpringerChamHeidelbergNewYorkDordrechtLondon ©SpringerInternationalPublishingSwitzerland2015 Thisworkissubjecttocopyright.AllrightsarereservedbythePublisher,whetherthewholeorpart of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilarmethodologynowknownorhereafterdeveloped. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publicationdoesnotimply,evenintheabsenceofaspecificstatement,thatsuchnamesareexempt fromtherelevantprotectivelawsandregulationsandthereforefreeforgeneraluse. Thepublisher,theauthorsandtheeditorsaresafetoassumethattheadviceandinformationinthis book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, express or implied, with respect to the material contained hereinorforanyerrorsoromissionsthatmayhavebeenmade. Printedonacid-freepaper Springer International Publishing AG Switzerland is part of Springer Science+Business Media (www.springer.com) Preface IgEantibodieswerediscoveredinthe1960sas“reaginicantibodies”(Ishizakaand Ishizaka1967),definedatthattimeasatypeofimmunoglobulinthatcouldtransfer hypersensitivitytoproteinantigens. Sincethen,thegenesandproteinsofbothIgE and its high-affinity receptor, FcεRI (Kinet 1999), have been fully characterized. TheroleofIgEinhumanchronicinflammatoryallergicdiseaseswassuggestedby alargenumberofassociationstudiesandwasmorerecentlyconclusivelyprovenby the beneficial effects of anti-IgE therapy in severe asthma. The study of IgE-producing B cells was nevertheless long hampered by their relative paucity in peripheral blood and lymphoid organs. The recent development of genetically modified mouse models to study IgE responses has enabled the trackingandisolationofIgE-expressingcellsandhasuncovereddistinctiveaspects of the IgE response. We now know that IgE cell responses are characterized by a transient IgE germinal center phase, a predominance of the IgE plasma cell fate, an absence offunctional IgE memory B cells, and the co-opting of the sequential switching process to generate high-affinity IgE antibodies. These findings have suggested a link between sequential switching to IgE and the pathogenic potential of IgE responses. Recent advances describing unique features of IgE cell differ- entiation and of the mechanisms involved in the memory of IgE responses are discussed in this volume by He Jin-shu and collaborators (“Biology of IgE Production: Ige Cell Differentiation and the Memory of Ige Responses”). IgE antibody genes are generated through class switch recombination (CSR), a process whereby the DNA sequence encoding the constant region of the IgE heavychain,Cε,isbroughtincloseproximitytotheVDJgenethroughloopingout, ligation, and excision of the intervening DNA sequences. Antibody genes can be further modified by somatic hypermutation (SH). Both CSR and SH are mediated bytheenzymeAID(Muramatsuetal.2000).HerePeiTongandDuaneWesemann discuss the molecular mechanisms underlying the generation of antibodies, how the specific features of CSR to IgE regulate the production of IgE antibodies in immatureandmatureBcells,andtheimplicationsofthisregulationfortherolesof IgE in disease (“Molecular Mechanisms of IgE Class Switch Recombination”). v vi Preface ThepathogenicpotentialofIgEantibodiesliesmainlyinitsabilitytobindtothe high-affinity FcεRI on the surface of mast cells and to induce mast cell degranu- lation upon crosslinking by allergens. Accordingly, it is now well established that IgEisavalidtherapeutictargetfordifficult-to-treatallergicinflammatory diseases, such as corticosteroid-resistant asthma. Stephanie Logsdon and Hans Oettgen (“Anti-IgE Therapy: Clinical Utility and Mechanistic Insights”) review the latest clinical data on the treatment of asthma and other allergic diseases with Omalizumab, the first therapeutic anti-IgE antibody successfully used in chronic allergic diseases.Immunological studies inanti-IgEtreated patients havealsoshed newlightontheroleofIgEinimmuneresponsesbeyondmastcellactivation, and the success of Omalizumab has reinvigorated the search for new approaches targeting IgE-FcεRI interactions. TheaffinityofIgEforanallergen,therelativeconcentrationofallergen-specific IgE in the total IgE pool, and IgE cross-reactivity, are all important determinants oftheoccurrence,ornot,ofallergicreactions.RyoSuzukiandcollaborators(“New Insights on the Signaling and Function of the High Affinity Receptor for IgE”) review the mechanisms of IgE- and FcεRI-mediated mast cell responses, sharing new insights into their modulation: we now know that monomeric IgE can induce diverse signaling and activation responses in mast cells, even in the absence of cognate antigens. New concepts have provided a framework linking monomeric IgE polyreactivity and its ability to activate mast cells in the absence of known antigen;furthermore,theaffinityofIgEhasbeenidentifiedasakeydeterminantin the type of signaling and inflammatory responses induced downstream of antigen recognition. The pathogenic role of IgE in allergy has somehow eclipsed its valuable pro- tective functions in the case of parasitic infection. Helminthes in particular induce the production of high levels of serum IgE, but their presence is, somewhat counterintuitively, associated with protection from allergic diseases, even in the presence of IgE antibodies against allergens. Firdaus Hamid and collaborators (“Helminth-Induced IgE and Protection Against Allergic Disorders”) discuss how helminthes infections result in the formation of IgE antibodies that recognize both theparasiteandtheallergen,buthavelowpathogenicpotential.Interestingly,there isevidenceofimportantdifferencesintheallergenepitopesrecognizedbyIgEfrom parasite-infected patients compared to allergic patients, and further research in this area holds the promise of exciting advances in our understanding of the mecha- nisms of allergy in the near future. The novel ideas emerging from these studies suggest new preventive and ther- apeutic approaches based on interventions that alter IgE concentration and its affinity for allergens. Alongsideprotectionfromparasites,IgE-mediatedmastcellresponsesappearto be animportantcomponent of ourbodies’ anti-tumor defenses.Lai Sum Leoh and collaborators (“IgE Immunotherapy Against Cancer”) explain the rationale behind theinnovativeuseofIgEratherthanIgGantibodiesincancertreatment,anddiscuss thetherapeuticIgEantibodiesthatarecurrentlyunderdevelopmentfortreatmentof Preface vii malignancies, as well as the possibility of prophylactic use of anti-tumor IgE and the challenges of effective delivery. We hope this volume on IgE antibodies will help to disseminate current knowledgeonthegenerationandfunctionofIgE,andencouragefurtherstudies.It isalsoouraimtoshowcasethebroadspectrumofIgEfunctions:incausing,aswell as preventing, allergic diseases; in defense against parasites, and as a valuable componentinprotectionfromcancer.Onlybytakingallthesefacetsofthecomplex biology of IgE into account can we hope to fully understand the workings of this intriguingbiologicalmoleculeandsoharnessitspotentialtoimprovehumanhealth. Juan J. Lafaille Maria A. Curotto de Lafaille References Ishizaka K, Ishizaka T (1967) Identification of gamma-E-antibodies as a carrier of reaginic activity.JImmunol99:1187–1198 Kinet JP (1999) The high-affinity IgE receptor (Fc epsilon RI): from physiology to pathology. AnnuRevImmunol17:931–972 Muramatsu M et al. (2000) Class switch recombination and hypermutation require activation- inducedcytidinedeaminase(AID),apotentialRNAeditingenzyme.Cell102:553–563 Contents Biology of IgE Production: IgE Cell Differentiation and the Memory of IgE Responses. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 Jin-Shu He, Sriram Narayanan, Sharrada Subramaniam, Wen Qi Ho, Juan J. Lafaille and Maria A. Curotto de Lafaille Molecular Mechanisms of IgE Class Switch Recombination. . . . . . . . . 21 Pei Tong and Duane R. Wesemann Anti-IgE Therapy: Clinical Utility and Mechanistic Insights . . . . . . . . 39 Stephanie L. Logsdon and Hans C. Oettgen New Insights on the Signaling and Function of the High-Affinity Receptor for IgE. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63 Ryo Suzuki, Jörg Scheffel and Juan Rivera Helminth-Induced IgE and Protection Against Allergic Disorders . . . . 91 Firdaus Hamid, Abena S. Amoah, Ronald van Ree and Maria Yazdanbakhsh IgE Immunotherapy Against Cancer . . . . . . . . . . . . . . . . . . . . . . . . . 109 Lai Sum Leoh, Tracy R. Daniels-Wells and Manuel L. Penichet Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 151 ix Biology of IgE Production: IgE Cell Differentiation and the Memory of IgE Responses Jin-ShuHe,SriramNarayanan,SharradaSubramaniam,WenQiHo, Juan J. Lafaille and Maria A. Curotto de Lafaille Abstract Thegenerationoflong-livedplasmacellsandmemoryBcellsproducing high-affinity antibodies depends on the maturation of B cell responses in germinal centers.Theseprocessesareessentialforlong-lastingantibody-mediatedprotection against infections. IgE antibodies are important for defense against parasites and toxins and can also mediate anti-tumor immunity. However, high-affinity IgE is alsothemainculpritresponsibleforthemanifestationsofallergicdisease,including life-threatening anaphylaxis. Thus, generation of high-affinity IgE must be tightly regulated.RecentstudiesofIgEBcellbiologyhaveunveiledtwomechanismsthat limithigh-affinityIgEmemoryresponses:First,Bcellsthathaverecentlyswitched to IgE production are programmed to rapidly differentiate into plasma cells, and second,IgEgerminalcentercellsaretransientandhighlyapoptotic.Opposingthese processes,wenowknowthatgerminalcenter-derivedIgGBcellscanswitchtoIgE production, effectively becoming IgE-producing plasma cells. In this chapter, we willdiscusstheuniquemolecularandcellularpathwaysinvolvedinthegeneration of IgE antibodies. J.-S.He(cid:1)S.Narayanan(cid:1)S.Subramaniam(cid:1)W.Q.Ho(cid:1)M.A.CurottodeLafaille(&) SingaporeImmunologyNetwork(SIgN),AgencyforScience,TechnologyandResearch, Singapore,Singapore e-mail:[email protected] S.Subramaniam NanyangTechnologicalUniversity,SchoolofBiologicalSciences,Singapore,Singapore J.J.Lafaille SkirballInstituteandDepartmentofPathology,NewYorkUniversitySchoolofMedicine, NewYork,USA ©SpringerInternationalPublishingSwitzerland2015 1 J.J.LafailleandM.A.CurottodeLafaille(eds.),IgEAntibodies:Generation andFunction,CurrentTopicsinMicrobiologyandImmunology388, DOI10.1007/978-3-319-13725-4_1
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