2023
Tracking 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 analysisMRNAHigh-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
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 sequencingCellsPostvaccinationDivergent 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 sequencing
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-LymphocytesCD4 AntigensDisease Models, AnimalEpitopesForkhead Transcription FactorsGerminal CenterHumansImmunityImmunologic MemoryInfluenza, HumanInfluenzavirus BIntegrasesMice, 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 centre
2017
Interleukin-10 from CD4+ follicular regulatory T cells promotes the germinal center response
Laidlaw BJ, Lu Y, Amezquita RA, Weinstein JS, Vander Heiden JA, Gupta NT, Kleinstein SH, Kaech SM, Craft J. Interleukin-10 from CD4+ follicular regulatory T cells promotes the germinal center response. Science Immunology 2017, 2 PMID: 29054998, PMCID: PMC5846620, DOI: 10.1126/sciimmunol.aan4767.Peer-Reviewed Original ResearchConceptsFollicular regulatory T cellsRegulatory T cellsIL-10Lymphocytic choriomeningitis virusT cellsB cellsInterleukin-10GC responseCell-derived IL-10Follicular helper T cellsHelper T cellsB cell responsesGerminal center responseGerminal center developmentActivated B cellsBox protein 1GC B cellsAcute infectionCenter responseCell responsesImportant mediatorNuclear translocationGC reactionProtein 1Forkhead box protein 1
2015
Salmonella Infection Drives Promiscuous B Cell Activation Followed by Extrafollicular Affinity Maturation
Di Niro R, Lee SJ, Vander Heiden J, Elsner RA, Trivedi N, Bannock JM, Gupta NT, Kleinstein SH, Vigneault F, Gilbert TJ, Meffre E, McSorley SJ, Shlomchik MJ. Salmonella Infection Drives Promiscuous B Cell Activation Followed by Extrafollicular Affinity Maturation. Immunity 2015, 43: 120-131. PMID: 26187411, PMCID: PMC4523395, DOI: 10.1016/j.immuni.2015.06.013.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, MonoclonalB-LymphocytesClonal Selection, Antigen-MediatedGerminal CenterImmunoglobulin GLymphocyte ActivationMiceMice, Inbred BALB CMice, Inbred C57BLMice, KnockoutReceptors, Antigen, B-CellSalmonella InfectionsSalmonella typhimuriumSomatic Hypermutation, ImmunoglobulinSpleenConceptsB cell receptorExtrafollicular sitesGerminal centersAffinity maturationInfection of miceB cell responsesB cell activationDetectable antibodiesSomatic hypermutationExtrafollicular responseAntigen microarraysSalmonella infectionAntigen targetsCell activationSalmonella typhimuriumCell responsesBCR specificityFlow cytometryCell receptorMonoclonal antibodiesUndetectable affinityClonal selectionInfectionAntibodiesLaser microdissectionResponsive population dynamics and wide seeding into the duodenal lamina propria of transglutaminase-2-specific plasma cells in celiac disease
Di Niro R, Snir O, Kaukinen K, Yaari G, Lundin K, Gupta N, Kleinstein S, Cols M, Cerutti A, Mäki M, Shlomchik M, Sollid L. Responsive population dynamics and wide seeding into the duodenal lamina propria of transglutaminase-2-specific plasma cells in celiac disease. Mucosal Immunology 2015, 9: 254-264. PMID: 26153762, PMCID: PMC4703456, DOI: 10.1038/mi.2015.57.Peer-Reviewed Original ResearchMeSH KeywordsAutoantibodiesBiopsyCeliac DiseaseCell CountDiet, Gluten-FreeDuodenumGene Expression RegulationGlutensGTP-Binding ProteinsHumansImmunoglobulin Heavy ChainsIntestinal MucosaLaser Capture MicrodissectionPlasma CellsProtein Glutamine gamma Glutamyltransferase 2Sequence Analysis, DNATransglutaminasesConceptsTG2-specific plasma cellsPlasma cellsCeliac diseaseLamina propriaTransglutaminase 2Antibody-mediated diseasesGluten-free dietSerum antibody levelsSerum antibody titersB cell responsesAntigen-specific antibodiesDuodenal lamina propriaGluten exposureUntreated patientsAntibody levelsAntibody titersCeliac lesionAntigen stainingSubepithelial layerAntibody productionIndividual biopsiesRepertoire analysisDiseaseGut tissueAntibodies
2013
The immune cell infiltrate populating meningiomas is composed of mature, antigen-experienced T and B cells
Fang L, Lowther DE, Meizlish ML, Anderson RC, Bruce JN, Devine L, Huttner AJ, Kleinstein SH, Lee JY, Stern JN, Yaari G, Lovato L, Cronk KM, O'Connor KC. The immune cell infiltrate populating meningiomas is composed of mature, antigen-experienced T and B cells. Neuro-Oncology 2013, 15: 1479-1490. PMID: 23978377, PMCID: PMC3813416, DOI: 10.1093/neuonc/not110.Peer-Reviewed Original ResearchConceptsTumor-infiltrating B cellsImmune cell infiltratesT cell repertoireCell infiltrateB cellsT cellsCell repertoireAntigen experienceImmune checkpoint molecules PD-1Memory/effector T cellsCheckpoint molecules PD-1Antigen-driven B cell responsesEffector T cell populationsTumor microenvironmentT-cell infiltratesRegulatory T cellsEffector T cellsT-cell phenotypeT cell populationsB cell responsesPeripheral blood lymphocytesAntigen-experienced CD4Cell populationsB cell populationsB cell repertoire