2024
Antibody gene features associated with binding and functional activity in malaria vaccine-derived human mAbs
Coelho C, Marquez S, Nguemwo Tentokam B, Berhe A, Miura K, Rao V, Long C, Doumbo O, Sagara I, Healy S, Kleinstein S, Duffy P. Antibody gene features associated with binding and functional activity in malaria vaccine-derived human mAbs. Npj Vaccines 2024, 9: 144. PMID: 39127706, PMCID: PMC11316794, DOI: 10.1038/s41541-024-00929-6.Peer-Reviewed Original ResearchHuman monoclonal antibodyBlocking parasite transmissionMalaria vaccinePlasmodium antigensImpact of adjuvantsClonotypic diversityHuman mAbsAS01Adjuvant groupVaccine designMalariaMonoclonal antibodiesAdjuvant selectionFunctional antibodiesAlhydrogelMAbGermline sequencesAntibodiesAntibody repertoireFunctional mAbsFunctional activityAdjuvantCohortIGHV1Vaccine
2022
Transcriptional atlas of the human immune response to 13 vaccines reveals a common predictor of vaccine-induced antibody responses
Hagan T, Gerritsen B, Tomalin LE, Fourati S, Mulè MP, Chawla DG, Rychkov D, Henrich E, Miller HER, Diray-Arce J, Dunn P, Lee A, Levy O, Gottardo R, Sarwal M, Tsang J, Suárez-Fariñas M, Sékaly R, Kleinstein S, Pulendran B. Transcriptional atlas of the human immune response to 13 vaccines reveals a common predictor of vaccine-induced antibody responses. Nature Immunology 2022, 23: 1788-1798. PMID: 36316475, PMCID: PMC9869360, DOI: 10.1038/s41590-022-01328-6.Peer-Reviewed Original ResearchConceptsAntibody responseDay 1Vaccine-induced antibodiesYellow fever vaccineHuman immune responseMechanisms of immunityB cell activationTranscriptional atlasFever vaccineDifferent vaccinesSystems vaccinologyImmune responseMost vaccinesDay 7Cell activationInnate immunityVaccineVaccinationImmunityCommon predictorsMolecular signaturesResponsePlasmablastsInterferonAntibodies
2018
AIRR Community Standardized Representations for Annotated Immune Repertoires
Vander Heiden J, Marquez S, Marthandan N, Bukhari SAC, Busse CE, Corrie B, Hershberg U, Kleinstein SH, Matsen F, Ralph DK, Rosenfeld AM, Schramm CA, Community T, Christley S, Laserson U. AIRR Community Standardized Representations for Annotated Immune Repertoires. Frontiers In Immunology 2018, 9: 2206. PMID: 30323809, PMCID: PMC6173121, DOI: 10.3389/fimmu.2018.02206.Peer-Reviewed Original Research
2016
Long-lived antigen-induced IgM plasma cells demonstrate somatic mutations and contribute to long-term protection
Bohannon C, Powers R, Satyabhama L, Cui A, Tipton C, Michaeli M, Skountzou I, Mittler RS, Kleinstein SH, Mehr R, Lee FE, Sanz I, Jacob J. Long-lived antigen-induced IgM plasma cells demonstrate somatic mutations and contribute to long-term protection. Nature Communications 2016, 7: 11826. PMID: 27270306, PMCID: PMC4899631, DOI: 10.1038/ncomms11826.Peer-Reviewed Original ResearchMeSH KeywordsAdoptive TransferAmino Acid MotifsAnimalsAntigensComplementarity Determining RegionsCytidine DeaminaseGerminal CenterImmunityImmunoglobulin Heavy ChainsImmunoglobulin MMice, Inbred C57BLMutationNeutralization TestsOrthomyxoviridaeOrthomyxoviridae InfectionsPlasma CellsSomatic Hypermutation, ImmunoglobulinSpleenConceptsIgM plasma cellsIgG plasma cellsPlasma cellsGerminal centersBone marrowLethal virus challengeProtective host immunitySomatic mutationsActivation-induced cytidine deaminaseHumoral immunityProtective antibodiesVirus challengeLong-term protectionHost immunityB cellsAffinity maturationMarrowLifelong sourceImmunityAntibodiesCellsCytidine deaminaseMutationsReplacement mutationsSpleen
2015
Neutralizing antibodies against West Nile virus identified directly from human B cells by single-cell analysis and next generation sequencing
Tsioris K, Gupta NT, Ogunniyi AO, Zimnisky RM, Qian F, Yao Y, Wang X, Stern JN, Chari R, Briggs AW, Clouser CR, Vigneault F, Church GM, Garcia MN, Murray KO, Montgomery RR, Kleinstein SH, Love JC. Neutralizing antibodies against West Nile virus identified directly from human B cells by single-cell analysis and next generation sequencing. Integrative Biology 2015, 7: 1587-1597. PMID: 26481611, PMCID: PMC4754972, DOI: 10.1039/c5ib00169b.Peer-Reviewed Original ResearchConceptsHumoral responseNext-generation sequencingB cellsWest Nile virus infectionSevere neurological illnessMemory B cellsAntibody-secreting cellsCohort of subjectsWNV-specific antibodiesHuman B cellsMosquito-borne diseaseWest Nile virusAnamnestic responseAntibody responseAvailable treatmentsClinical severityAntibody isotypesNeurological illnessVaccine studiesVirus infectionGeneration sequencingInfectious diseasesPrevious exposureTherapeutic antibodiesAntibodiesSalmonella 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 tissueAntibodiesLong-lived IgM plasma cells confer host protection against viral challenge (LYM6P.717)
Bohannon C, Powers R, Satyabhama L, Cui A, Tipton C, Michaeli M, Mehr R, Mittler R, Kleinstein S, Sanz I, Jacob J. Long-lived IgM plasma cells confer host protection against viral challenge (LYM6P.717). The Journal Of Immunology 2015, 194: 135.5-135.5. DOI: 10.4049/jimmunol.194.supp.135.5.Peer-Reviewed Original Research
2014
Shared VH1-46 gene usage by pemphigus vulgaris autoantibodies indicates common humoral immune responses among patients
Cho MJ, Lo AS, Mao X, Nagler AR, Ellebrecht CT, Mukherjee EM, Hammers CM, Choi EJ, Sharma PM, Uduman M, Li H, Rux AH, Farber SA, Rubin CB, Kleinstein SH, Sachais BS, Posner MR, Cavacini LA, Payne AS. Shared VH1-46 gene usage by pemphigus vulgaris autoantibodies indicates common humoral immune responses among patients. Nature Communications 2014, 5: 4167. PMID: 24942562, PMCID: PMC4120239, DOI: 10.1038/ncomms5167.Peer-Reviewed Original ResearchConceptsHumoral immune responsePemphigus vulgarisGene usageImmune responseAnti-Dsg3 antibodiesSomatic mutationsRequirement of mutationsPemphigus vulgaris autoantibodiesBlistering diseasePV patientsVH gene usagePatientsDesmoglein 3Unrelated patientsAutoAbsAutoantibodiesAutoreactivityDsg3MutationsGermline sequencesAbReplacement mutationsVDJ recombinationDiseaseAntibodies