Featured Publications
Maturation of germinal center B cells after influenza virus vaccination in humans
McIntire K, Meng H, Lin T, Kim W, Moore N, Han J, McMahon M, Wang M, Malladi S, Mohammed B, Zhou J, Schmitz A, Hoehn K, Carreño J, Yellin T, Suessen T, Middleton W, Teefey S, Presti R, Krammer F, Turner J, Ward A, Wilson I, Kleinstein S, Ellebedy A. Maturation of germinal center B cells after influenza virus vaccination in humans. Journal Of Experimental Medicine 2024, 221: e20240668. PMID: 38935072, PMCID: PMC11211068, DOI: 10.1084/jem.20240668.Peer-Reviewed Original ResearchConceptsB cellsInfluenza vaccineGerminal centersAntigen-specific GC B cellsResponse to seasonal influenza vaccinationLong-lived bone marrow plasma cellsResponse to influenza vaccinationBone marrow plasma cellsGerminal center B cellsGC B cell clonesInfluenza virus vaccineMaturation of B cellsMarrow plasma cellsSeasonal influenza vaccineMemory B cellsHemagglutinin (HAB cell clonesGC B cellsInfluenza hemagglutinin (HAH5 HANeedle aspirationLymphoid structuresLymph nodesPlasma cellsGC reaction
2024
Inferring B Cell Phylogenies from Paired H and L Chain BCR Sequences with Dowser.
Jensen C, Sumner J, Kleinstein S, Hoehn K. Inferring B Cell Phylogenies from Paired H and L Chain BCR Sequences with Dowser. The Journal Of Immunology 2024, 212: 1579-1588. PMID: 38557795, PMCID: PMC11073909, DOI: 10.4049/jimmunol.2300851.Peer-Reviewed Original ResearchConceptsPhylogenetic treeL chainsBranch lengthsBCR sequencesTree-building methodsSingle-cell sequencing dataHistory of mutationsSingle-cell sequencingPhylogenetic methodsSequence dataSequencing technologiesL chain sequencesTree accuracyEvolutionary processSingle-cellPhylogenyImmune responseSomatic hypermutationSequenceClonesMutationsB cell clonesHuman immune responseTreesBCR
2023
Age-associated B cells are heterogeneous and dynamic drivers of autoimmunity in mice
Nickerson K, Smita S, Hoehn K, Marinov A, Thomas K, Kos J, Yang Y, Bastacky S, Watson C, Kleinstein S, Shlomchik M. Age-associated B cells are heterogeneous and dynamic drivers of autoimmunity in mice. Journal Of Experimental Medicine 2023, 220: e20221346. PMID: 36828389, PMCID: PMC9997508, DOI: 10.1084/jem.20221346.Peer-Reviewed Original Research
2022
Reemergence of pathogenic, autoantibody-producing B cell clones in myasthenia gravis following B cell depletion therapy
Fichtner ML, Hoehn KB, Ford EE, Mane-Damas M, Oh S, Waters P, Payne AS, Smith ML, Watson CT, Losen M, Martinez-Martinez P, Nowak RJ, Kleinstein SH, O’Connor K. Reemergence of pathogenic, autoantibody-producing B cell clones in myasthenia gravis following B cell depletion therapy. Acta Neuropathologica Communications 2022, 10: 154. PMID: 36307868, PMCID: PMC9617453, DOI: 10.1186/s40478-022-01454-0.Peer-Reviewed Original ResearchConceptsB cell depletion therapyB cell clonesMuSK-MG patientsMyasthenia gravisB cellsMG patientsDepletion therapyCell clonesAutoantibody-producing B cellsMuscle-specific tyrosine kinaseComplete stable remissionB cell receptor repertoireCell receptor repertoireValuable candidate biomarkersB cell receptorMG relapseClinical relapseStable remissionDisease relapseAutoimmune disordersRelapsePatientsAcetylcholine receptorsCandidate biomarkersReceptor repertoireSingle-cell multi-omics reveals dyssynchrony of the innate and adaptive immune system in progressive COVID-19
Unterman A, Sumida TS, Nouri N, Yan X, Zhao AY, Gasque V, Schupp JC, Asashima H, Liu Y, Cosme C, Deng W, Chen M, Raredon MSB, Hoehn KB, Wang G, Wang Z, DeIuliis G, Ravindra NG, Li N, Castaldi C, Wong P, Fournier J, Bermejo S, Sharma L, Casanovas-Massana A, Vogels CBF, Wyllie AL, Grubaugh ND, Melillo A, Meng H, Stein Y, Minasyan M, Mohanty S, Ruff WE, Cohen I, Raddassi K, Niklason L, Ko A, Montgomery R, Farhadian S, Iwasaki A, Shaw A, van Dijk D, Zhao H, Kleinstein S, Hafler D, Kaminski N, Dela Cruz C. Single-cell multi-omics reveals dyssynchrony of the innate and adaptive immune system in progressive COVID-19. Nature Communications 2022, 13: 440. PMID: 35064122, PMCID: PMC8782894, DOI: 10.1038/s41467-021-27716-4.Peer-Reviewed Original ResearchMeSH KeywordsAdaptive ImmunityAgedAntibodies, Monoclonal, HumanizedCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCells, CulturedCOVID-19COVID-19 Drug TreatmentFemaleGene Expression ProfilingGene Expression RegulationHumansImmunity, InnateMaleReceptors, Antigen, B-CellReceptors, Antigen, T-CellRNA-SeqSARS-CoV-2Single-Cell AnalysisConceptsProgressive COVID-19B cell clonesSingle-cell analysisT cellsImmune responseMulti-omics single-cell analysisCOVID-19Cell clonesAdaptive immune interactionsSevere COVID-19Dynamic immune responsesGene expressionSARS-CoV-2 virusAdaptive immune systemSomatic hypermutation frequenciesCellular effectsProtein markersEffector CD8Immune signaturesProgressive diseaseHypermutation frequencyProgressive courseClassical monocytesClonesImmune interactions
2021
B Cell Mobilization, Dissemination, Fine Tuning of Local Antigen Specificity and Isotype Selection in Asthma
Ohm-Laursen L, Meng H, Hoehn KB, Nouri N, Jiang Y, Clouser C, Johnstone TG, Hause R, Sandhar BS, Upton NEG, Chevretton EB, Lakhani R, Corrigan CJ, Kleinstein SH, Gould HJ. B Cell Mobilization, Dissemination, Fine Tuning of Local Antigen Specificity and Isotype Selection in Asthma. Frontiers In Immunology 2021, 12: 702074. PMID: 34721376, PMCID: PMC8552043, DOI: 10.3389/fimmu.2021.702074.Peer-Reviewed Original ResearchConceptsLower respiratory tractRespiratory tractB cellsAtopic asthmaPlasma cellsCommon respiratory tract diseaseB-cell mobilizationNon-atopic controlsRespiratory tract mucosaUpper respiratory tractRespiratory tract diseaseOrgan-specific diseasesAntibody repertoireB cell clonesAdaptive immune receptor repertoire sequencingBronchial mucosaNasal mucosaTract diseaseCell mobilizationIsotype selectionAntigen specificityAdult volunteersMucosal surfacesImmune systemAsthma
2020
Thymus-derived B cell clones persist in the circulation after thymectomy in myasthenia gravis
Jiang R, Hoehn KB, Lee CS, Pham MC, Homer RJ, Detterbeck FC, Aban I, Jacobson L, Vincent A, Nowak RJ, Kaminski HJ, Kleinstein SH, O'Connor KC. Thymus-derived B cell clones persist in the circulation after thymectomy in myasthenia gravis. Proceedings Of The National Academy Of Sciences Of The United States Of America 2020, 117: 30649-30660. PMID: 33199596, PMCID: PMC7720237, DOI: 10.1073/pnas.2007206117.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAutoantibodiesB-LymphocytesBiomarkersClonal EvolutionClonal Selection, Antigen-MediatedDisease SusceptibilityFemaleHumansLymphocyte CountMaleMiddle AgedModels, BiologicalMyasthenia GravisRadioimmunoassayReceptors, CholinergicThymectomyThymus GlandV(D)J RecombinationYoung AdultConceptsB cell clonesMyasthenia gravisB cell repertoireB cellsCell clonesPlasma cellsCell repertoireAdditional immunosuppressive treatmentDiminished clinical responseThymic lymphofollicular hyperplasiaComplete stable remissionMajority of patientsAntigen-experienced B cellsRandomized clinical trialsClinical symptom measuresAChR autoantibodiesImmunosuppressive treatmentSteroid doseAutoantibody titersMG thymusClinical responseStable remissionClinical scoresAutoimmune diseasesClinical trialsHuman 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 centreSingle-cell repertoire tracing identifies rituximab-resistant B cells during myasthenia gravis relapses
Jiang R, Fichtner ML, Hoehn KB, Pham MC, Stathopoulos P, Nowak RJ, Kleinstein SH, O'Connor KC. Single-cell repertoire tracing identifies rituximab-resistant B cells during myasthenia gravis relapses. JCI Insight 2020, 5 PMID: 32573488, PMCID: PMC7453893, DOI: 10.1172/jci.insight.136471.Peer-Reviewed Original ResearchConceptsMuscle-specific kinase myasthenia gravisMemory B cellsB cell subsetsAntibody-secreting cellsB cellsCell subsetsAutoantibody-producing B cellsB-cell depleting therapyCell-depleting therapyB cell clonesB cell survivalGene expression signaturesMyasthenia gravisAutoimmune disordersRelapseB cell samplesReceptor profilingCell clonesExpression signaturesRituximabTherapyCell survivalCellsTreatmentCell samples
2018
Local Clonal Diversification and Dissemination of B Lymphocytes in the Human Bronchial Mucosa
Ohm-Laursen L, Meng H, Chen J, Zhou JQ, Corrigan CJ, Gould HJ, Kleinstein SH. Local Clonal Diversification and Dissemination of B Lymphocytes in the Human Bronchial Mucosa. Frontiers In Immunology 2018, 9: 1976. PMID: 30245687, PMCID: PMC6137163, DOI: 10.3389/fimmu.2018.01976.Peer-Reviewed Original ResearchConceptsHumoral immune responseBronchial mucosaB cell repertoireHealthy subjectsAsthmatic patientsImmune responseCell repertoireAdaptive humoral immune responseB cell antibody productionFeatures of atopyB cell clonesHuman bronchial mucosaMucosal migrationAdaptive immune receptor repertoire sequencingAtopic asthmaAsthmatic individualsBronchial biopsiesRight lungPeripheral bloodDistal biopsiesAdjacent biopsiesLarge cohortB cellsB lymphocytesAntibody production