2025
Circulating immunoregulatory B cell and autoreactive antibody profiles predict lack of toxicity to anti-PD-1 checkpoint inhibitor treatment in advanced melanoma
Willsmore Z, Booth L, Patel A, Di Meo A, Prassas I, Chauhan J, Wu Y, Fitzpartick A, Stoker K, Kapiris M, Biswas D, Perucha E, Whittaker S, Tsoka S, Diamandis E, Middleton G, Tull T, Papa S, Lacy K, Karagiannis S. Circulating immunoregulatory B cell and autoreactive antibody profiles predict lack of toxicity to anti-PD-1 checkpoint inhibitor treatment in advanced melanoma. Journal For ImmunoTherapy Of Cancer 2025, 13: e011682. PMID: 40449958, PMCID: PMC12142029, DOI: 10.1136/jitc-2025-011682.Peer-Reviewed Original ResearchConceptsImmune-related adverse eventsAnti-PD-1 therapyStage III/IV melanomaAnti-PD-1Memory B cellsB cellsCheckpoint inhibitorsHigher IgG4Development of immune-related adverse eventsResponse to anti-PD-1 therapyClass-switched memory B cellsClass-switched B cellsAccurate predictive biomarkersDN2 B cellsExtrafollicular B cell responseCheckpoint inhibitor treatmentB cell frequenciesB cell responsesIL-10+Response to therapyIgE serum levelsImmune response profileHumoral immune response profileSerum antibody isotypesAdvanced melanoma
2024
Booster COVID-19 mRNA vaccination ameliorates impaired B-cell but not T-cell responses in older adults
Kometani K, Yorimitsu T, Jo N, Yamaguchi E, Kikuchi O, Fukahori M, Sawada T, Tsujimoto Y, Sunami A, Li M, Ito T, Pretemer Y, Gao Y, Hidaka Y, Yamamoto M, Kaku N, Nakagama Y, Kido Y, Grifoni A, Sette A, Nagao M, Morita S, Nakajima T, Muto M, Hamazaki Y. Booster COVID-19 mRNA vaccination ameliorates impaired B-cell but not T-cell responses in older adults. Frontiers In Immunology 2024, 15: 1455334. PMID: 39717779, PMCID: PMC11663736, DOI: 10.3389/fimmu.2024.1455334.Peer-Reviewed Original ResearchMeSH KeywordsAdultAge FactorsAgedAged, 80 and overAntibodies, ViralB-LymphocytesCD8-Positive T-LymphocytesCOVID-19COVID-19 VaccinesFemaleHumansImmunity, HumoralImmunization, SecondaryImmunoglobulin GImmunologic MemoryMaleMemory B CellsMiddle AgedmRNA VaccinesSARS-CoV-2Spike Glycoprotein, CoronavirusYoung AdultConceptsB cell responsesT cell responsesB cellsT cellsBooster vaccinationT cell-mediated cellular immunityCD8<sup>+</sup> T cell responsesCytotoxic CD8<sup>+</sup> T cell responsesReduced PD-1 expressionMemory T cell activationMemory B cell responsesCOVID-19 mRNA booster vaccinationPD-1 expressionCOVID-19 mRNA vaccinesMemory T cellsImpaired humoral immunityImpaired B cellYoung adultsT cell activationMRNA booster vaccinationEnhanced IgG responseSpike-specificCellular immunityMRNA vaccinesAge-associated differencesSUMO-specific protease 1 regulates germinal center B cell response through deSUMOylation of PAX5
Qi J, Yan L, Sun J, Huang C, Su B, Cheng J, Shen L. SUMO-specific protease 1 regulates germinal center B cell response through deSUMOylation of PAX5. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 121: e2314619121. PMID: 38776375, PMCID: PMC11145296, DOI: 10.1073/pnas.2314619121.Peer-Reviewed Original ResearchConceptsPaired box protein 5GC B cellsSUMO-specific protease 1Activation-induced cytidine deaminaseProtein SUMOylationClass switch recombinationProtein stabilityB cellsProtease 1B cell responsesProtein 5Cytidine deaminaseSENP1Up-regulatedGC B cell responsesSomatic hypermutationSUMOylationDeSUMOylationGerminal centersHigher affinityProduction of class-switched antibodiesGerminal center B cell responsesGC reactionMemory B cellsClass-switched antibodiesCholera toxin and O-specific polysaccharide immune responses after oral cholera vaccination with Dukoral in different age groups of Bangladeshi participants
Dash P, Hakim A, Akter A, Banna H, Kaisar M, Aktar A, Jahan S, Ferdous J, Basher S, Kamruzzaman M, Chowdhury F, Akter A, Tauheed I, Weil A, Charles R, Calderwood S, Ryan E, LaRocque R, Harris J, Bhuiyan T, Qadri F. Cholera toxin and O-specific polysaccharide immune responses after oral cholera vaccination with Dukoral in different age groups of Bangladeshi participants. MSphere 2024, 9: e00565-23. PMID: 38391226, PMCID: PMC10964428, DOI: 10.1128/msphere.00565-23.Peer-Reviewed Original ResearchB cell responsesMemory B cell responsesClass-switched antibody responsesOral cholera vaccineAntibody responseImmune responseCholera toxin B subunitCholera vaccineToxin B subunitAge groupsAnti-OSPOlder childrenPrevent choleraIgG antibody responsesYoung childrenB subunitVaccine seriesSignificant IgAIgM responseWhole-cellOlder vaccineesCholera toxinIgAVaccineIgG
2023
Polyinosinic: polycytidylic acid induced inflammation enhances while lipopolysaccharide diminishes alloimmunity to platelet transfusion in mice
Tran J, Muench M, Gaillard B, Darst O, Tomayko M, Jackman R. Polyinosinic: polycytidylic acid induced inflammation enhances while lipopolysaccharide diminishes alloimmunity to platelet transfusion in mice. Frontiers In Immunology 2023, 14: 1281130. PMID: 38146372, PMCID: PMC10749330, DOI: 10.3389/fimmu.2023.1281130.Peer-Reviewed Original ResearchConceptsB cell responsesPlatelet transfusionsMajor histocompatibility complexCell responsesPrior exposurePlatelet alloimmunizationMemory B cell responsesPlatelet transfusion recipientsSubsequent platelet transfusionsAllogeneic platelet transfusionsNegative bacterial infectionsPolyinosinic-polycytidylic acidGerminal center formationPrior inflammationAlloantibody responsesAlloimmune responsePlatelet refractorinessFuture transplantTransfusion recipientsMHC tetramersAdverse reactionsInflammatory environmentAntigen experiencePlatelet antigensTransfusionElevated glucose metabolism driving pro-inflammatory response in B cells contributes to the progression of type 1 diabetes
Li Z, Zhao M, Li J, Luo W, Huang J, Huang G, Xie Z, Xiao Y, Huang J, Li X, Zhao B, Zhou Z. Elevated glucose metabolism driving pro-inflammatory response in B cells contributes to the progression of type 1 diabetes. Clinical Immunology 2023, 255: 109729. PMID: 37562723, DOI: 10.1016/j.clim.2023.109729.Peer-Reviewed Original ResearchConceptsType 1 diabetesPro-inflammatory responseB cellsGlucose metabolismCytokine productionAberrant B cell responsesNon-obese diabetic (NOD) micePro-inflammatory cytokine productionHigh blood glucose levelsOnset of diabetesInflammatory cytokine productionAdaptive immune responsesB cell responsesCross-sectional cohortImmune system failureDiabetic mouse modelB cell functionBlood glucose levelsB cell populationsB cell metabolismPancreatic beta cellsB cell proliferationElevated glucose metabolismInsulitis developmentNOD miceTracking B cell responses to the SARS-CoV-2 mRNA-1273 vaccine
de Assis F, Hoehn K, Zhang X, Kardava L, Smith C, Merhebi O, Buckner C, Trihemasava K, Wang W, Seamon C, Chen V, Schaughency P, Cheung F, Martins A, Chiang C, Li Y, Tsang J, Chun T, Kleinstein S, Moir S. Tracking B cell responses to the SARS-CoV-2 mRNA-1273 vaccine. Cell Reports 2023, 42: 112780. PMID: 37440409, PMCID: PMC10529190, DOI: 10.1016/j.celrep.2023.112780.Peer-Reviewed Original ResearchConceptsMemory B cellsB cell receptorB cellsAtypical memory B cellsInfection-naïve individualsTwo-dose SARSSARS-CoV-2 mRNAB cell responsesAntibody-secreting cellsMonth 6Protective immunityCell responsesCell receptorClonal expansionImmunoglobulin GEarly timepointsLater timepointsPlasmablastsVaccinationCD71TimepointsSurface proteinsCellsMultimodal single-cell analysisMRNADistinct metabolic requirements regulate B cell activation and germinal center responses
Sharma R, Smolkin R, Chowdhury P, Fernandez K, Kim Y, Cols M, Alread W, Yen W, Hu W, Wang Z, Violante S, Chaligné R, Li M, Cross J, Chaudhuri J. Distinct metabolic requirements regulate B cell activation and germinal center responses. Nature Immunology 2023, 24: 1358-1369. PMID: 37365386, PMCID: PMC11262065, DOI: 10.1038/s41590-023-01540-y.Peer-Reviewed Original ResearchNaïve B cellsB cellsGerminal centersB cell-dependent immune responsesExtrafollicular B cell responsesCell-dependent immune responsesB cell responsesGerminal center responseB cell activationMetabolic requirementsAntibody responseDistinct metabolic requirementsHigh-affinity antibodiesT cellsExtrafollicular sitesImmune responseProliferating lymphocytesCenter responseClonal proliferationCell activationCell responsesGC reactionLactate dehydrogenaseAerobic glycolysisNaïveHigh-throughput single-cell profiling of B cell responses following inactivated influenza vaccination in young and older adults
Wang M, Jiang R, Mohanty S, Meng H, Shaw A, Kleinstein S. High-throughput single-cell profiling of B cell responses following inactivated influenza vaccination in young and older adults. Aging 2023, 15: 9250-9274. PMID: 37367734, PMCID: PMC10564424, DOI: 10.18632/aging.204778.Peer-Reviewed Original ResearchConceptsB cellsActivated B cellsB cell receptorOlder adultsInfluenza vaccinationAge groupsPeripheral blood B cellsYoung adultsInactivated influenza vaccineB cell responsesSubstantial disease burdenBlood B cellsMemory B cellsInfluenza vaccination responsesStrong antibody responseAge-related changesInfluenza vaccineVaccination responseSeasonal influenzaAntibody responseHospital visitsDisease burdenSomatic hypermutation frequenciesVaccinationCell responses
2022
Diverging regulation of Bach2 protein and RNA expression determine cell fate in early B cell response
Hu Q, Xu T, Zhang M, Zhang H, Liu Y, Li H, Chen C, Zheng J, Zhang Z, Li F, Shen N, Zhang W, Melnick A, Huang C. Diverging regulation of Bach2 protein and RNA expression determine cell fate in early B cell response. Cell Reports 2022, 40: 111035. PMID: 35793628, PMCID: PMC9550188, DOI: 10.1016/j.celrep.2022.111035.Peer-Reviewed Original ResearchConceptsBach2 proteinCell fateActivated B cellsMemory B cellsB cellsCell fate choiceDetermines cell fateCell fate outcomesRapamycin complex 1B cell fateEffector cellsGerminal centre B cell fatePivotal transcription factorB cell receptor affinityEarly B cell responsesTranscription factorsDependent translationB cell responsesPrimary humoral responseGC fateMechanistic targetHumoral responseProteinPlasma cellsDifferential dynamicsHigh-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
Human B cell lineages associated with germinal centers following influenza vaccination are measurably evolving
Hoehn KB, Turner JS, Miller FI, Jiang R, Pybus OG, Ellebedy A, Kleinstein SH. Human B cell lineages associated with germinal centers following influenza vaccination are measurably evolving. ELife 2021, 10: e70873. PMID: 34787567, PMCID: PMC8741214, DOI: 10.7554/elife.70873.Peer-Reviewed Original ResearchConceptsSeasonal influenza vaccinationInfluenza vaccinationB-cell lineageGerminal centersB cell evolutionPoor efficacyB cellsSeasonal influenza virus vaccinationSeasonal influenza virus vaccinesVaccine-induced B cell responsesInfluenza virus vaccinationInfluenza virus vaccinePre-existing immunityB cell responsesMemory B cellsCell lineagesGC B cellsSeasonal vaccinationHIV infectionVirus vaccinationVirus vaccineVaccinationVaccine antigensCell responsesSignificant heterogeneityCutting Edge: Distinct B Cell Repertoires Characterize Patients with Mild and Severe COVID-19
Hoehn KB, Ramanathan P, Unterman A, Sumida TS, Asashima H, Hafler DA, Kaminski N, Dela Cruz CS, Sealfon SC, Bukreyev A, Kleinstein SH. Cutting Edge: Distinct B Cell Repertoires Characterize Patients with Mild and Severe COVID-19. The Journal Of Immunology 2021, 206: 2785-2790. PMID: 34049971, PMCID: PMC8627528, DOI: 10.4049/jimmunol.2100135.Peer-Reviewed Original ResearchConceptsSevere COVID-19Mild COVID-19B cell responsesMemory B cellsB cell repertoireB cellsCell repertoireCOVID-19Cell responsesExtrafollicular B cell responsesLong-term immunitySymptomatic COVID-19Onset of symptomsB cell populationsGerminal center reactionProtective immunityPlasma cellsSingle-cell RNA sequencingCenter reactionPatientsCell populationsImmunityRNA sequencingCellsPostvaccinationT Follicular Regulatory Cells: Choreographers of Productive Germinal Center Responses
Lu Y, Craft J. T Follicular Regulatory Cells: Choreographers of Productive Germinal Center Responses. Frontiers In Immunology 2021, 12: 679909. PMID: 34177925, PMCID: PMC8222975, DOI: 10.3389/fimmu.2021.679909.Peer-Reviewed Original ResearchConceptsTfr cellsTreg cellsHumoral immunityGerminal centersAntigen-specific B cell responsesFollicular helper cellsFollicular regulatory (Tfr) cellsB cell folliclesRegulatory T cellsB cell autoreactivityB cell responsesGerminal center responseB cell toleranceVaccine design strategiesTranscription factor Bcl6Regulatory cellsHelper cellsImmune homeostasisProductive immunityT cellsViral infectionCenter responseCell responsesGC responseImmune challengeDivergent and self-reactive immune responses in the CNS of COVID-19 patients with neurological symptoms
Song E, Bartley CM, Chow RD, Ngo TT, Jiang R, Zamecnik CR, Dandekar R, Loudermilk RP, Dai Y, Liu F, Sunshine S, Liu J, Wu W, Hawes IA, Alvarenga BD, Huynh T, McAlpine L, Rahman NT, Geng B, Chiarella J, Goldman-Israelow B, Vogels CBF, Grubaugh ND, Casanovas-Massana A, Phinney BS, Salemi M, Alexander JR, Gallego JA, Lencz T, Walsh H, Wapniarski AE, Mohanty S, Lucas C, Klein J, Mao T, Oh J, Ring A, Spudich S, Ko AI, Kleinstein SH, Pak J, DeRisi JL, Iwasaki A, Pleasure SJ, Wilson MR, Farhadian SF. Divergent and self-reactive immune responses in the CNS of COVID-19 patients with neurological symptoms. Cell Reports Medicine 2021, 2: 100288. PMID: 33969321, PMCID: PMC8091032, DOI: 10.1016/j.xcrm.2021.100288.Peer-Reviewed Original ResearchNeurological symptomsImmune responseCerebrospinal fluidAnti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodiesCOVID-19Self-reactive immune responsesSARS-CoV-2 antibodiesCompartmentalized immune responseCSF immunoglobulin GRole of autoimmunityCOVID-19 patientsB cell responsesCoronavirus disease 2019Immune surveyNeurologic sequelaePulmonary infectionBrain infectionSerum antibodiesDisease 2019Monoclonal antibody targetsAnimal modelsTarget epitopesCell activationCell responsesSingle-cell RNA sequencingNeoantigen driven B cell and CD4+ T follicular helper cell collaboration promotes robust anti-tumor CD8+ T cell responses
Cui C, Joshi N, Craft J. Neoantigen driven B cell and CD4+ T follicular helper cell collaboration promotes robust anti-tumor CD8+ T cell responses. The Journal Of Immunology 2021, 206: 57.01-57.01. DOI: 10.4049/jimmunol.206.supp.57.01.Peer-Reviewed Original ResearchT cell responsesAnti-tumor CD8Tfh cellsB cellsCell responsesIL-21Cell collaborationProtective anti-tumor responsesTfh-B cell interactionsTumor-specific B cellsGC B cell responsesTumor-specific CD4Anti-tumor immunityFavorable clinical outcomeAnti-tumor responseIL-21 receptorB cell responsesLung adenocarcinoma patientsAnalysis of survivalT cell-B cell interactionsGerminal center formationCell interactionsGC B cellsAbstract CD4Effector CD8Type I Interferon–Activated STAT4 Regulation of Follicular Helper T Cell–Dependent Cytokine and Immunoglobulin Production in Lupus
Dong X, Antao OQ, Song W, Sanchez GM, Zembrzuski K, Koumpouras F, Lemenze A, Craft J, Weinstein JS. Type I Interferon–Activated STAT4 Regulation of Follicular Helper T Cell–Dependent Cytokine and Immunoglobulin Production in Lupus. Arthritis & Rheumatology 2021, 73: 478-489. PMID: 33512094, PMCID: PMC7914134, DOI: 10.1002/art.41532.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnimalsAntibody FormationAutoantibodiesB-LymphocytesCase-Control StudiesCytokinesDisease Models, AnimalFemaleHumansImmunoglobulinsInterferon Type IInterferon-gammaInterleukinsLupus Erythematosus, SystemicMaleMice, Inbred MRL lprMiddle AgedRNA-SeqSTAT4 Transcription FactorT Follicular Helper CellsConceptsSystemic lupus erythematosusTfh-like cellsTfh cellsIL-21Human lupusDisease activityCytokine productionSTAT4 activationImmunoglobulin productionPathogenic B cell responsesCourse of lupusClinical disease activityT cell secretionLupus-prone miceHealthy control subjectsCourse of diseaseB cell responsesCytokine interleukin-21Potential therapeutic targetType I IFNB cell maturationSLE patientsPathogenic cytokinesLupus erythematosusInterleukin-21
2020
CD4+ follicular regulatory T cells optimize the influenza virus–specific B cell response
Lu Y, Jiang R, Freyn AW, Wang J, Strohmeier S, Lederer K, Locci M, Zhao H, Angeletti D, O’Connor K, Kleinstein SH, Nachbagauer R, Craft J. CD4+ follicular regulatory T cells optimize the influenza virus–specific B cell response. Journal Of Experimental Medicine 2020, 218: e20200547. PMID: 33326020, PMCID: PMC7748821, DOI: 10.1084/jem.20200547.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibody FormationAntigensB-LymphocytesBetainfluenzavirusCD4 AntigensDisease Models, AnimalEpitopesForkhead Transcription FactorsGerminal CenterHumansImmunityImmunologic MemoryInfluenza, HumanIntegrasesMice, Inbred C57BLOrthomyxoviridae InfectionsReceptors, Antigen, B-CellSpecies SpecificityT-Lymphocytes, RegulatoryVaccinationConceptsB cell responsesGerminal center B cell responsesFollicular regulatory T cellsRegulatory T cellsTfr cellsCell responsesT cellsViral challengeHumoral memoryVirus-specific B cell responsesAntigen-specific B cell responsesFollicular helper T cellsHA stalk regionHelper T cellsInfluenza virus infectionGerminal center developmentAntibody responsePlasma cellsVirus infectionImmunization modelAntibody productionBCR repertoireInfluenza virusRepeated exposureInfluenza virus glycoproteinsHuman germinal centres engage memory and naive B cells after influenza vaccination
Turner JS, Zhou JQ, Han J, Schmitz AJ, Rizk AA, Alsoussi WB, Lei T, Amor M, McIntire KM, Meade P, Strohmeier S, Brent RI, Richey ST, Haile A, Yang YR, Klebert MK, Suessen T, Teefey S, Presti RM, Krammer F, Kleinstein SH, Ward AB, Ellebedy AH. Human germinal centres engage memory and naive B cells after influenza vaccination. Nature 2020, 586: 127-132. PMID: 32866963, PMCID: PMC7566073, DOI: 10.1038/s41586-020-2711-0.Peer-Reviewed Original ResearchConceptsB cell clonesInfluenza vaccinationGerminal center B cellsB cellsGerminal center reactionCell clonesLymph nodesMonoclonal antibodiesPre-existing memory B cellsGerminal center B cell responsesStrain-specific monoclonal antibodiesCenter reactionUltrasound-guided fine-needle aspirationMajor public health threatEarly plasmablast responsesInfluenza virus vaccinationSeasonal influenza vaccinationCross-reactive monoclonal antibodiesB cell responsesMemory B cellsB-cell originFine-needle aspirationNaive B cellsPublic health threatHuman germinal centreEvidence for a pathogenic role of extrafollicular, IL-10–producing CCR6+B helper T cells in systemic lupus erythematosus
Facciotti F, Larghi P, Bosotti R, Vasco C, Gagliani N, Cordiglieri C, Mazzara S, Ranzani V, Rottoli E, Curti S, Penatti A, Karnani B, Kobayashi Y, Crosti M, Bombaci M, van Hamburg JP, Rossetti G, Gualtierotti R, Gerosa M, Gatti S, Torretta S, Pignataro L, Tas SW, Abrignani S, Pagani M, Grassi F, Meroni PL, Flavell RA, Geginat J. Evidence for a pathogenic role of extrafollicular, IL-10–producing CCR6+B helper T cells in systemic lupus erythematosus. Proceedings Of The National Academy Of Sciences Of The United States Of America 2020, 117: 7305-7316. PMID: 32184325, PMCID: PMC7132288, DOI: 10.1073/pnas.1917834117.Peer-Reviewed Original ResearchConceptsSystemic lupus erythematosusHelper T cellsT cellsIL-10Pathogenic roleSLE patientsLupus erythematosusIL-7RB cellsPathogenic anti-dsDNA antibodiesFollicular helper T cellsAnti-dsDNA antibodiesLupus-like diseaseT cell populationsB cell responsesProduction ex vivoCytokine reporter miceProminent pathogenic roleImmunoglobulin G productionNaïve B cellsIL-17Antiinflammatory cytokinesLymph nodesInterleukin-10Peripheral blood
This site is protected by hCaptcha and its Privacy Policy and Terms of Service apply