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 ResearchConceptsB-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 blockingPD-1highCXCR5–CD4+ peripheral helper T cells promote CXCR3+ plasmablasts in human acute viral infection
Asashima H, Mohanty S, Comi M, Ruff W, Hoehn K, Wong P, Klein J, Lucas C, Cohen I, Coffey S, Lele N, Greta L, Raddassi K, Chaudhary O, Unterman A, Emu B, Kleinstein S, Montgomery R, Iwasaki A, Dela Cruz C, Kaminski N, Shaw A, Hafler D, Sumida T. PD-1highCXCR5–CD4+ peripheral helper T cells promote CXCR3+ plasmablasts in human acute viral infection. Cell Reports 2023, 42: 111895. PMID: 36596303, PMCID: PMC9806868, DOI: 10.1016/j.celrep.2022.111895.Peer-Reviewed Original ResearchConceptsAcute viral infectionTph cellsViral infectionCXCR3 expressionClinical outcomesHelper TSevere viral infectionsB cell helpBetter clinical outcomesProtective humoral immunityT cell-B cell interactionsKey immune responsesPlasmablast expansionB cell differentiationCell subsetsHumoral immunityCell helpImmune responseInterferon γPlasmablast differentiationB cellsPlasmablastsCell responsesInfectionCD4
2022
Glycan-specific B-1 cells mediate blockade of endogenous retroviruses emergence through recognition of conserved glycan epitopes
Yang Y, Treger R, Hernandez-Bird J, Iwasaki A. Glycan-specific B-1 cells mediate blockade of endogenous retroviruses emergence through recognition of conserved glycan epitopes. The Journal Of Immunology 2022, 208: 126.31-126.31. DOI: 10.4049/jimmunol.208.supp.126.31.Peer-Reviewed Original ResearchB-1 cellsB cell populationsB cellsEndogenous retrovirusesCell-intrinsic controlNatural antibodiesImmunodeficient miceUnimmunized miceGlycan-specific antibodiesClonal repertoirePleural cavityRepertoire profilingViral antigensBlockadeComplement pathwayVH genesCell compartmentAntibodiesGlycan epitopesMiceRetrovirusesAbstract Endogenous retrovirusesEpitopesSensor stimulationCells
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 responseLesionsGlycan-reactive natural antibodies mediate blockade of endogenous retroviruses emergence
Yang Y, Treger R, Hernandez-Bird J, Iwasaki A. Glycan-reactive natural antibodies mediate blockade of endogenous retroviruses emergence. The Journal Of Immunology 2021, 206: 114.09-114.09. DOI: 10.4049/jimmunol.206.supp.114.09.Peer-Reviewed Original ResearchB-1 cellsB cell populationsB cellsNatural antibodiesEndogenous retrovirusesCell-intrinsic controlImmunodeficient miceSelf-antigensUnimmunized miceFetal haematopoiesisGlycan-specific antibodiesClonal repertoirePleural cavityRepertoire profilingViral antigensBlockadeComplement pathwayVH genesCell compartmentAntibodiesCell-specificAbstract Endogenous retrovirusesMiceGenetic invadersVertebrate genomes
2019
Murine Leukemia Virus Exploits Innate Sensing by Toll-Like Receptor 7 in B-1 Cells To Establish Infection and Locally Spread in Mice
Pi R, Iwasaki A, Sewald X, Mothes W, Uchil PD. Murine Leukemia Virus Exploits Innate Sensing by Toll-Like Receptor 7 in B-1 Cells To Establish Infection and Locally Spread in Mice. Journal Of Virology 2019, 93: 10.1128/jvi.00930-19. PMID: 31434732, PMCID: PMC6803250, DOI: 10.1128/jvi.00930-19.Peer-Reviewed Original ResearchConceptsPopliteal lymph nodesFriend murine leukemia virusInnate immune sensing pathwaysToll-like receptor 7Viral spreadMurine leukemia virusCell-deficient miceType I interferon responseWild-type miceCell populationsType I interferonLeukemia virusRobust virus replicationI interferon responseAntiviral intervention strategiesInfected cell typesSentinel macrophagesAdoptive transferCell typesLymph nodesReceptor 7Virus infectionInnate sensingB cellsI interferonMigrant 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
2018
1 Type I Interferon Is Necessary and Sufficient for Alloimmunization to Transfused KEL-Expressing RBCs in Mice
Gibb D, Liu J, Natarajan P, Santhanakrishnan M, Madrid D, Eisenbarth S, Zimring J, Iwasaki A, Hendrickson J. 1 Type I Interferon Is Necessary and Sufficient for Alloimmunization to Transfused KEL-Expressing RBCs in Mice. American Journal Of Clinical Pathology 2018, 149: s163-s163. DOI: 10.1093/ajcp/aqx149.370.Peer-Reviewed Original ResearchIFNα/βAlloimmune responseType I interferonKEL RBCsRBC alloimmunizationWT miceIFNAR1 expressionInflammatory stimuliB cellsI interferonChimeric miceRBC antigensNew transgenic mouse modelCertain inflammatory disordersHuman KEL glycoproteinRed blood cell antigensIFNα/β productionToll-like receptorsInterferon regulatory factor 3Transgenic mouse modelBlood cell antigensRegulatory factor 3Non-hematopoietic cellsIgG alloantibodiesTransfusion protocol
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
CD301b+ dendritic cells suppress T follicular helper cells and antibody responses to protein antigens
Kumamoto Y, Hirai T, Wong PW, Kaplan DH, Iwasaki A. CD301b+ dendritic cells suppress T follicular helper cells and antibody responses to protein antigens. ELife 2016, 5: e17979. PMID: 27657168, PMCID: PMC5033605, DOI: 10.7554/elife.17979.Peer-Reviewed Original ResearchDendritic cellsAntibody responsePD-L1Protein antigensBlocking PD-1Follicular helper cellsPD-1 ligandsStrong antibody responseWild-type miceGerminal center B cellsTfh cellsPD-1Cell primingIgG responsesHelper cellsPD-L2Autoantibody generationSuccessful vaccineCD301bB cellsTransient depletionAntigenMiceAntibodiesNovel regulatory mechanism
2014
Innate immunity to influenza virus infection
Iwasaki A, Pillai PS. Innate immunity to influenza virus infection. Nature Reviews Immunology 2014, 14: 315-328. PMID: 24762827, PMCID: PMC4104278, DOI: 10.1038/nri3665.Peer-Reviewed Original ResearchConceptsInfluenza virus infectionToll-like receptor 7T cell responsesVirus infectionInterferon-stimulated genesIL-1βNLRP3 inflammasomeViral challengeB cellsCell responsesHigh-dose viral challengeInfluenza virusAntiviral B cellsMultiple pattern recognition receptorsPlasmacytoid dendritic cellsAdaptive immune responsesInfected cellsRetinoic acid-inducible gene IAirway epithelial cellsAcid-inducible gene IPattern recognition receptorsInfluenza virus-infected cellsVirus-infected cellsAntiviral defense genesDendritic cells
2011
CD4+ T cells support cytotoxic T lymphocyte priming by controlling lymph node input
Kumamoto Y, Mattei LM, Sellers S, Payne GW, Iwasaki A. CD4+ T cells support cytotoxic T lymphocyte priming by controlling lymph node input. Proceedings Of The National Academy Of Sciences Of The United States Of America 2011, 108: 8749-8754. PMID: 21555577, PMCID: PMC3102372, DOI: 10.1073/pnas.1100567108.Peer-Reviewed Original ResearchConceptsT cellsDendritic cellsCytotoxic T-lymphocyte primingT lymphocyte responsesAntigen-specific CTLsT lymphocyte primingSecondary lymphoid organsT cell helpCD40-dependent mannerNaïve B cellsCognate CTLsAcute infectionLymph nodesLymphocyte primingLymphocyte responsesLymphocyte recruitmentCTL expansionLymphoid organsImmune responseNaïve precursorsB cellsImmune systemReactive LNsIntracellular pathogensInfection
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
2003
CD11b+ Peyer’s Patch Dendritic Cells Secrete IL-6 and Induce IgA Secretion from Naive B Cells
Sato A, Hashiguchi M, Toda E, Iwasaki A, Hachimura S, Kaminogawa S. CD11b+ Peyer’s Patch Dendritic Cells Secrete IL-6 and Induce IgA Secretion from Naive B Cells. The Journal Of Immunology 2003, 171: 3684-3690. PMID: 14500666, DOI: 10.4049/jimmunol.171.7.3684.Peer-Reviewed Original ResearchConceptsPP dendritic cellsNaive B cellsDendritic cellsIL-6B cellsIgA secretionDC subsetsIgA productionPeyer's patch dendritic cellsSecrete IL-6Exogenous IL-6Cell coculture systemDC populationsLymphoid organsCytokine secretionAb productionT cellsHigh levelsSpleenSecretionCoculture systemCellsIgAUnique roleDistinct capacities
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