2024
A B cell screen against endogenous retroviruses identifies glycan-reactive IgM that recognizes a broad array of enveloped viruses
Yang Y, Treger R, Hernandez-Bird J, Lu P, Mao T, Iwasaki A. A B cell screen against endogenous retroviruses identifies glycan-reactive IgM that recognizes a broad array of enveloped viruses. Science Immunology 2024, 9: eadd6608. PMID: 39514636, DOI: 10.1126/sciimmunol.add6608.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, ViralB-LymphocytesEndogenous RetrovirusesImmunoglobulin MMiceMice, Inbred C57BLPolysaccharidesConceptsB-1 cellsB cell-deficient miceEndogenous retrovirusesEnveloped virusesNatural IgM antibodiesGermline-encoded antibodiesNaive miceInnate antiviral mechanismsGenetic invadersB cellsVertebrate genomesNatural antibody repertoireRepertoire profilingSurface antigensInfectious endogenous retrovirusIgM antibodiesSelf-proteinsComplement pathwayAntibody repertoireAntibodiesMiceRetrovirusesVirusSensor stimulationGlycoprotein
2023
Mature B cells and mesenchymal stem cells control emergency myelopoiesis
Lim V, Feng X, Miao R, Zehentmeier S, Ewing-Crystal N, Lee M, Tumanov A, Oh J, Iwasaki A, Wang A, Choi J, Pereira J. Mature B cells and mesenchymal stem cells control emergency myelopoiesis. Life Science Alliance 2023, 6: e202301924. PMID: 36717247, PMCID: PMC9889502, DOI: 10.26508/lsa.202301924.Peer-Reviewed Original ResearchConceptsMarrow mesenchymal stem cellsSystemic inflammationMature B cellsB cellsEmergency myelopoiesisMesenchymal stem cellsIL-1 receptorBone marrow mesenchymal stem cellsStem cellsMyeloid cell productionMonocyte numbersB lineage cellsCCL2 productionViral infectionLymphotoxin α1β2InflammationReduced survivalLymphopoietic activityMyelopoiesisLymphopoiesisImportant regulatorLTβRCell productionCellsGenetic blocking
2022
High-affinity, neutralizing antibodies to SARS-CoV-2 can be made without T follicular helper cells
Chen JS, Chow RD, Song E, Mao T, Israelow B, Kamath K, Bozekowski J, Haynes WA, Filler RB, Menasche BL, Wei J, Alfajaro MM, Song W, Peng L, Carter L, Weinstein JS, Gowthaman U, Chen S, Craft J, Shon JC, Iwasaki A, Wilen CB, Eisenbarth SC. High-affinity, neutralizing antibodies to SARS-CoV-2 can be made without T follicular helper cells. Science Immunology 2022, 7: eabl5652. PMID: 34914544, PMCID: PMC8977051, DOI: 10.1126/sciimmunol.abl5652.Peer-Reviewed Original ResearchConceptsSARS-CoV-2 infectionSARS-CoV-2Follicular helper cellsB cell responsesHelper cellsAntibody productionCell responsesSARS-CoV-2 vaccinationB-cell receptor sequencingSevere COVID-19Cell receptor sequencingIndependent antibodiesT cell-B cell interactionsViral inflammationAntiviral antibodiesImmunoglobulin class switchingVirus infectionGerminal centersViral infectionClonal repertoireInfectionAntibodiesClass switchingCOVID-19Patients
2021
Intranasal priming induces local lung-resident B cell populations that secrete protective mucosal antiviral IgA
Oh JE, Song E, Moriyama M, Wong P, Zhang S, Jiang R, Strohmeier S, Kleinstein SH, Krammer F, Iwasaki A. Intranasal priming induces local lung-resident B cell populations that secrete protective mucosal antiviral IgA. Science Immunology 2021, 6: eabj5129. PMID: 34890255, PMCID: PMC8762609, DOI: 10.1126/sciimmunol.abj5129.Peer-Reviewed Original ResearchConceptsVirus infectionIgA secretionB cellsMucosal surfacesIgA-secreting B cellsIgA-expressing cellsRole of IgARespiratory virus infectionsIgA-secreting cellsLower respiratory tractInfluenza virus infectionEffective immune protectionHeterologous virus infectionMemory B cellsSecretory immunoglobulin AProtein-based vaccinesB cell populationsPredominant Ig isotypeSite of entryIntranasal primingBronchoalveolar spaceProtective immunityVaccine strategiesRespiratory mucosaImmune protectionB cells join T cell clusters in the host response to recurrent herpes simplex virus 2 infection
Gehlhausen JR, Iwasaki A. B cells join T cell clusters in the host response to recurrent herpes simplex virus 2 infection. Journal Of Clinical Investigation 2021, 131: e148300. PMID: 33938452, PMCID: PMC8087191, DOI: 10.1172/jci148300.Peer-Reviewed Original ResearchConceptsAntibody-secreting cellsB cellsRecurrent lesionsHerpes simplex virus 2 infectionHSV-2-specific antibodiesRecurrent genital herpes lesionsSimplex virus 2 infectionGenital herpes lesionsHSV-2 lesionsVirus 2 infectionT cell clustersSkin biopsy specimensB cell subsetsB cell populationsNaive B cellsStage of infectionLesion reactivationDisease resolutionImmune infiltratesAntibody levelsHerpes lesionsCell subsetsBiopsy specimensHost responseLesions
2019
Migrant memory B cells secrete luminal antibody in the vagina
Oh JE, Iijima N, Song E, Lu P, Klein J, Jiang R, Kleinstein SH, Iwasaki A. Migrant memory B cells secrete luminal antibody in the vagina. Nature 2019, 571: 122-126. PMID: 31189952, PMCID: PMC6609483, DOI: 10.1038/s41586-019-1285-1.Peer-Reviewed Original ResearchConceptsMemory B cellsFemale reproductive tractB cellsPlasma cellsReproductive tractCD4 tissue-resident memory T cellsTissue-resident memory T cellsLower female reproductive tractHerpes simplex virus 2Genital herpes infectionMemory T cellsExpression of chemokinesSimplex virus 2CXCR3-dependent mannerLocal plasma cellsLuminal antibodyMucosal antibodiesHerpes infectionPrimary infectionMucosal barrierSecondary challengeVariety of pathogensT cellsLamina propriaInducible source
2017
B cells require Type 1 interferon to produce alloantibodies to transfused KEL‐expressing red blood cells in mice
Gibb DR, Liu J, Santhanakrishnan M, Natarajan P, Madrid DJ, Patel S, Eisenbarth SC, Tormey CA, Stowell SR, Iwasaki A, Hendrickson JE. B cells require Type 1 interferon to produce alloantibodies to transfused KEL‐expressing red blood cells in mice. Transfusion 2017, 57: 2595-2608. PMID: 28836263, PMCID: PMC5745367, DOI: 10.1111/trf.14288.Peer-Reviewed Original ResearchConceptsBone marrow chimeric miceHuman KEL glycoproteinType 1 interferonB cellsMean fluorescence intensityChimeric miceRed blood cell antigensBlood cell antigensGerminal center B cellsWT B cellsRBC alloimmunizationIgG alloantibodiesAlloimmune responseB cell differentiationRed blood cellsTransfusion protocolControl miceInflammatory stateWT miceAutoimmune pathologyIgG productionIFNAR1 expressionPlasma cellsAntiviral immunityInflammatory stimuli
2016
Access of protective antiviral antibody to neuronal tissues requires CD4 T-cell help
Iijima N, Iwasaki A. Access of protective antiviral antibody to neuronal tissues requires CD4 T-cell help. Nature 2016, 533: 552-556. PMID: 27225131, PMCID: PMC4883597, DOI: 10.1038/nature17979.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, ViralBiological TransportBlood-Brain BarrierB-LymphocytesCapillary PermeabilityCD4-Positive T-LymphocytesDisease Models, AnimalFemaleGanglia, SpinalHerpes GenitalisHerpesvirus 2, HumanHistocompatibility Antigens Class IImmunologic MemoryIntegrin alpha4Interferon-gammaMiceNerve TissueNervous SystemNeuronsNoseReceptors, FcSpinal CordVesiculovirus
2009
[Mucosal immune defense against sexually transmitted diseases].
Iijima N, Iwasaki A. [Mucosal immune defense against sexually transmitted diseases]. Clinical Journal Of Japan 2009, 67: 2-4. PMID: 19177745.Peer-Reviewed Original Research
2008
Dendritic cells and B cells maximize mucosal Th1 memory response to herpes simplex virus
Iijima N, Linehan MM, Zamora M, Butkus D, Dunn R, Kehry MR, Laufer TM, Iwasaki A. Dendritic cells and B cells maximize mucosal Th1 memory response to herpes simplex virus. Journal Of Experimental Medicine 2008, 205: 3041-3052. PMID: 19047439, PMCID: PMC2605233, DOI: 10.1084/jem.20082039.Peer-Reviewed Original ResearchConceptsMemory Th1 cellsDendritic cellsTh1 cellsB cellsIFN-gammaHerpes simplex virus 2 infectionAntiviral protectionSimplex virus 2 infectionMemory CD4 T cellsFurther viral replicationTh1 memory responseHSV-2 infectionCD4 T cellsLocal dendritic cellsVirus 2 infectionAntigen-presenting cellsCytotoxic T lymphocytesMHC class IISite of infectionHerpes simplex virusTh1 responseImmunized miceRecall responsesViral antigensMHC classThe autophagy gene ATG5 plays an essential role in B lymphocyte development
Miller BC, Zhao Z, Stephenson LM, Cadwell K, Pua HH, Lee HK, Mizushima NN, Iwasaki A, He YW, Swat W, Virgin HW. The autophagy gene ATG5 plays an essential role in B lymphocyte development. Autophagy 2008, 4: 309-314. PMID: 18188005, DOI: 10.4161/auto.5474.Peer-Reviewed Original ResearchConceptsB cell developmentCell developmentGene ATG5Pre-B cell transitionB lymphocyte developmentDeletion of Atg5Fetal liver progenitorsAutophagy gene ATG5B cell survivalCell lineagesCell transitionLymphocyte developmentCell survivalB-1a B cellsCell deathCre-loxP technologyCytoplasmic constituentsATG5Liver progenitorsEssential roleSignificant defectsB cellsDiscrete stagesCell numberCells
2004
Toll-like receptor control of the adaptive immune responses
Iwasaki A, Medzhitov R. Toll-like receptor control of the adaptive immune responses. Nature Immunology 2004, 5: 987-995. PMID: 15454922, DOI: 10.1038/ni1112.Peer-Reviewed Original ResearchConceptsToll-like receptorsAdaptive immune responsesImmune responseMechanisms of TLRToll-like receptor controlHost defense responsesDendritic cell functionDendritic cell populationsMicrobial infectionsInnate immune systemDistinct anatomical locationsInflammatory reactionAdaptive immunityImmune systemAnatomical locationReceptor controlCell functionCell populationsMultiple mechanismsInfectionRecent studiesResponseInitiationSystemic defenseImportant clues
2002
The CXC Chemokine Murine Monokine Induced by IFN-γ (CXC Chemokine Ligand 9) Is Made by APCs, Targets Lymphocytes Including Activated B Cells, and Supports Antibody Responses to a Bacterial Pathogen In Vivo
Park MK, Amichay D, Love P, Wick E, Liao F, Grinberg A, Rabin RL, Zhang HH, Gebeyehu S, Wright TM, Iwasaki A, Weng Y, DeMartino JA, Elkins KL, Farber JM. The CXC Chemokine Murine Monokine Induced by IFN-γ (CXC Chemokine Ligand 9) Is Made by APCs, Targets Lymphocytes Including Activated B Cells, and Supports Antibody Responses to a Bacterial Pathogen In Vivo. The Journal Of Immunology 2002, 169: 1433-1443. PMID: 12133969, DOI: 10.4049/jimmunol.169.3.1433.Peer-Reviewed Original ResearchConceptsT cellsActivated B cellsB cellsDendritic cellsIFN-gammaIntracellular bacterium Francisella tularensis live vaccine strainChemotactic factorsCell activationFrancisella tularensis live vaccine strainRole of MIGT cell infiltrationTularensis live vaccine strainOptimal humoral responsesLive vaccine strainT cell activationB cell activationHuman T cellsReceptor CXCR3Humoral responseCell infiltrationLymphoid organsTarget lymphocytesCXC chemokinesInflammatory reactionPeripheral tissues