2023
The Plasma Cell Infiltrate Populating the Muscle Tissue of Patients with Inclusion Body Myositis Features Distinct B Cell Receptor Repertoire Properties
Jiang R, Roy B, Wu Q, Mohanty S, Nowak R, Shaw A, Kleinstein S, O’Connor K. The Plasma Cell Infiltrate Populating the Muscle Tissue of Patients with Inclusion Body Myositis Features Distinct B Cell Receptor Repertoire Properties. ImmunoHorizons 2023, 7: 310-322. PMID: 37171806, PMCID: PMC10579972, DOI: 10.4049/immunohorizons.2200078.Peer-Reviewed Original ResearchConceptsInclusion body myositisMemory B cellsCell infiltrateBody myositisB cellsIBM muscle biopsiesB-cell infiltratesPlasma cell infiltrateClass-switched IgGMuscle tissueAdaptive immune receptor repertoire sequencingHumoral responseHealthy controlsIgA isotypePlasma cellsCell repertoireMuscle biopsyInfiltratesDegenerative disordersDisease pathologyRepertoire sequencingSkeletal muscleDermatomyositisPolymyositisMyositisPD-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
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 ResearchMeSH KeywordsAntibodiesAntigensAsthmaB-LymphocytesBronchiCell MovementHumansImmunoglobulin DNasal MucosaPlasma CellsConceptsLower 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 systemAsthmaHeterogeneity of meningeal B cells reveals a lymphopoietic niche at the CNS borders
Brioschi S, Wang WL, Peng V, Wang M, Shchukina I, Greenberg ZJ, Bando JK, Jaeger N, Czepielewski RS, Swain A, Mogilenko DA, Beatty WL, Bayguinov P, Fitzpatrick JAJ, Schuettpelz LG, Fronick CC, Smirnov I, Kipnis J, Shapiro VS, Wu GF, Gilfillan S, Cella M, Artyomov MN, Kleinstein SH, Colonna M. Heterogeneity of meningeal B cells reveals a lymphopoietic niche at the CNS borders. Science 2021, 373 PMID: 34083450, PMCID: PMC8448524, DOI: 10.1126/science.abf9277.Peer-Reviewed Original ResearchConceptsCentral nervous systemMeningeal B cellsB cellsAdaptive immune cellsAntigen-experienced B cellsBone marrow chimerasCNS bordersCNS antigensBlood borneImmune privilegeImmune cellsBone marrow nicheParabiosis experimentsSystemic circulationNervous systemB cell developmentLymphopoietic nicheMeningesMarrow nicheVascular connectionsCell developmentCellsConfocal imagingCalvariaImmunosurveillanceImmune dysregulation and autoreactivity correlate with disease severity in SARS-CoV-2-associated multisystem inflammatory syndrome in children
Ramaswamy A, Brodsky NN, Sumida TS, Comi M, Asashima H, Hoehn KB, Li N, Liu Y, Shah A, Ravindra NG, Bishai J, Khan A, Lau W, Sellers B, Bansal N, Guerrerio P, Unterman A, Habet V, Rice AJ, Catanzaro J, Chandnani H, Lopez M, Kaminski N, Dela Cruz CS, Tsang JS, Wang Z, Yan X, Kleinstein SH, van Dijk D, Pierce RW, Hafler DA, Lucas CL. Immune dysregulation and autoreactivity correlate with disease severity in SARS-CoV-2-associated multisystem inflammatory syndrome in children. Immunity 2021, 54: 1083-1095.e7. PMID: 33891889, PMCID: PMC8043654, DOI: 10.1016/j.immuni.2021.04.003.Peer-Reviewed Original ResearchConceptsMIS-C patientsDisease severityInflammatory syndromeTCR repertoireSARS-CoV-2-associated multisystem inflammatory syndromeAsymptomatic SARS-CoV-2 infectionSARS-CoV-2 infectionAdult COVID-19Post-infectious complicationsMultisystem inflammatory syndromeCytotoxicity genesHealthy pediatricImmune dysregulationMemory TActive infectionMyeloid dysfunctionPatientsSingle-cell RNA sequencingFlow cytometrySerum proteomicsRepertoire analysisElevated expressionSeverityAlarminsCOVID-19
2016
Generation of Long-Lived Bone Marrow Plasma Cells Secreting Antibodies Specific for the HIV-1 gp41 Membrane-Proximal External Region in the Absence of Polyreactivity
Donius LR, Cheng Y, Choi J, Sun ZY, Hanson M, Zhang M, Gierahn TM, Marquez S, Uduman M, Kleinstein SH, Irvine D, Love JC, Reinherz EL, Kim M. Generation of Long-Lived Bone Marrow Plasma Cells Secreting Antibodies Specific for the HIV-1 gp41 Membrane-Proximal External Region in the Absence of Polyreactivity. Journal Of Virology 2016, 90: 8875-8890. PMID: 27466419, PMCID: PMC5021391, DOI: 10.1128/jvi.01089-16.Peer-Reviewed Original ResearchConceptsMPER-specific antibodiesAntigen specificityB cellsAntigen-specific antibody responsesHIV-1 gp41 membrane-proximal external regionAmino acid sequenceBone marrow plasmaEffective preventive vaccineHIV-1 bnAbsHIV-1 cladesHIV-1 pandemicGp41 membrane-proximal external regionAnti-MPER antibodiesContext of lipidPositive selectionRegion amino acid sequencesSelective pressureAcid sequenceMembrane-proximal external regionMarrow plasmaPreventive vaccineAntibody responseBiophysical characterizationPlasma cellsVaccine formulationsLong-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
Responsive 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