2025
Luck gone cold: A trifecta of B cell mutations associates with cryoglobulinemia.
Chen K, O'Connor K. Luck gone cold: A trifecta of B cell mutations associates with cryoglobulinemia. Science Immunology 2025, 10: eadx6827. PMID: 40184441, DOI: 10.1126/sciimmunol.adx6827.Peer-Reviewed Original ResearchConceptsAutoreactive B cellsSomatic mutationsAssociated with cryoglobulinemiaB cellsMutationsAutoimmune diseases
2024
Aberrant zonal recycling of germinal center B cells impairs appropriate selection in lupus
Sanchez G, Hirsch E, VanValkenburg A, Mayer D, Gbedande K, Francis R, Song W, Antao O, Brimmer K, Lemenze A, Stephens R, Johnson W, Weinstein J. Aberrant zonal recycling of germinal center B cells impairs appropriate selection in lupus. Cell Reports 2024, 43: 114978. PMID: 39527476, PMCID: PMC11682828, DOI: 10.1016/j.celrep.2024.114978.Peer-Reviewed Original ResearchGerminal centersB cellsDifferentiation of autoreactive B cellsLoss of MYCResponse to CD40 signalingPolyclonal B cell activationB cell dysregulationAccumulation of plasma cellsAutoreactive B cellsB cell activationGC B cellsB cell cycleProduction of autoantibodiesB cell signalingDecreased mutation frequencyRepertoire diversityPlasma cellsAutoimmune diseasesPersistent infectionCD40 SignalingDisease progressionMutation frequencyReduced proliferationLupusLight zone
2023
CD25 recruits inhibitory phosphatases for feedback control of B-cell receptor signaling
Sun R, Lee J, Robinson M, Kume K, Cosgun K, Chan L, Leveille E, Geng H, Vykunta V, Shy B, Marson A, Meffre E, Müschen M. CD25 recruits inhibitory phosphatases for feedback control of B-cell receptor signaling. The Journal Of Immunology 2023, 210: 154.23-154.23. DOI: 10.4049/jimmunol.210.supp.154.23.Peer-Reviewed Original ResearchAntigen-experienced B cellsB cellsEarly B cell developmentGerminal centersB cell developmentSpontaneous germinal centersCD25 surface expressionAutoreactive B cellsRole of CD25B cell toleranceB-cell receptor signalingB-cell leukemiaB cell receptorAutoantibody productionCD25Cell toleranceGenetic ablationReceptor signalingBCR signalingOncogenic signalingInhibitorySuccessful initiationSignalingNegative selectionAutoimmunityAge-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
2021
Pharmacological Targeting of PI3K-Dependent Central Tolerance Mechanisms in Refractory Pre-Germinal Center B-Cell Malignancies
Kume K, Lee J, Chan L, Robinson M, Cosgun K, Meffre E, Müschen M. Pharmacological Targeting of PI3K-Dependent Central Tolerance Mechanisms in Refractory Pre-Germinal Center B-Cell Malignancies. Blood 2021, 138: 2267. DOI: 10.1182/blood-2021-149806.Peer-Reviewed Original ResearchCentral tolerance mechanismsMantle cell lymphomaB-cell malignanciesAutoreactive B cellsB cellsB cell developmentB cell receptorEarly B cell developmentB-ALLClinical cohortPharmacological targetingPathological signalingU-CLLNormal B-cell activationAutoreactive B cell receptorsRefractory B-ALLSequential treatment regimensPI3KNegative B cell selectionChronic lymphocytic leukemiaLarge clinical cohortB cell activationB-cell tumorsHuman B lymphopoiesisB cell selectionMetabolic determinants of B-cell selection
Chan LN, Aghania E, Leveille E, Müschen M. Metabolic determinants of B-cell selection. Biochemical Society Transactions 2021, 49: 1467-1478. PMID: 34196360, DOI: 10.1042/bst20201316.BooksConceptsB cellsAutoimmune diseasesB cell selectionB cell developmentImmune systemNegative B cell selectionRisk of developmentAutoreactive B cellsB-cell malignanciesAdaptive immune protectionAdaptive immune systemAntibody-producing cellsPremalignant B cellsEarly B cell developmentHarmful autoantibodiesHigh-affinity antibodiesImmune protectionAutoreactive clonesChronic restrictionBone marrowMalignant transformationMetabolic determinantsDiseaseLymphomaLeukemia
2020
Monovalent IgG4 autoantibodies require self-antigen driven affinity maturation to acquire pathogenic capacity
Fichtner M, Vieni C, Redler R, Jiang R, Suarez P, Nowak R, Burden S, Bhabha G, Ekiert D, O’Connor K. Monovalent IgG4 autoantibodies require self-antigen driven affinity maturation to acquire pathogenic capacity. The Journal Of Immunology 2020, 204: 224.39-224.39. DOI: 10.4049/jimmunol.204.supp.224.39.Peer-Reviewed Original ResearchMuSK myasthenia gravisMyasthenia gravisUnmutated common ancestorPathogenic capacityB-cell-mediated autoimmune diseasesAntigen-driven affinity maturationCell-mediated autoimmune diseaseMuscle-specific tyrosine kinaseSubset of patientsAutoreactive B cellsMonovalent antigen-binding fragmentsAffinity maturationHuman monoclonal autoantibodiesUnique autoantibodiesIgG4 autoantibodiesPathogenic autoantibodiesAutoimmune disordersAutoimmune responseAutoimmune diseasesSelf antigensIgG4 subclassAutoantibodiesMG autoantibodiesB cellsFab-arm exchange
2019
The Contribution of B Cells in Autoimmune Liver Diseases
Taylor SA, Assis DN, Mack CL. The Contribution of B Cells in Autoimmune Liver Diseases. Seminars In Liver Disease 2019, 39: 422-431. PMID: 31226726, PMCID: PMC6800599, DOI: 10.1055/s-0039-1688751.BooksConceptsAutoimmune liver diseaseT cell activationB cellsLiver diseaseT cellsCell activationB-cell mechanismsRegulatory T cellsProduction of autoantibodiesAutoreactive T cellsAutoreactive B cellsGeneration of cytokinesAutoimmune hepatitisCell mechanismsAntigen presentationDisease pathogenesisAutoantibodiesDiseaseCellsActivationVast majorityHepatitisCholangiopathyAutoimmunityCytokines
2018
Autoimmunity Checkpoints As Therapeutic Targets in B-Cell Malignancies
Chen Z, Muschen M. Autoimmunity Checkpoints As Therapeutic Targets in B-Cell Malignancies. Blood 2018, 132: 1587. DOI: 10.1182/blood-2018-99-113674.Peer-Reviewed Original ResearchAutoreactive B-cell antigen receptorsB-cell malignanciesAcute lymphoblastic leukemiaAutoreactive B cellsB cellsCell malignanciesB cell antigen receptorNormal B cellsTypes of cancerAIC activationTargeted therapyAutoreactive clonesMalignant transformationTargeted activationAutoreactive B lymphocytesLymphocyte developmentPI3KB-cell lymphomaB-lymphoid malignanciesB-cell receptor signalingDrug-resistant leukemiaB-cell leukemiaB-cell tumorsCell deathNegative selection
2016
PTPN22 inhibition resets defective human central B cell tolerance
Schickel JN, Kuhny M, Baldo A, Bannock JM, Massad C, Wang H, Katz N, Oe T, Menard L, Soulas-Sprauel P, Strowig T, Flavell R, Meffre E. PTPN22 inhibition resets defective human central B cell tolerance. Science Immunology 2016, 1 PMID: 27917411, PMCID: PMC5127630, DOI: 10.1126/sciimmunol.aaf7153.Peer-Reviewed Original ResearchThe microRNA miR-148a functions as a critical regulator of B cell tolerance and autoimmunity
Gonzalez-Martin A, Adams BD, Lai M, Shepherd J, Salvador-Bernaldez M, Salvador JM, Lu J, Nemazee D, Xiao C. The microRNA miR-148a functions as a critical regulator of B cell tolerance and autoimmunity. Nature Immunology 2016, 17: 433-440. PMID: 26901150, PMCID: PMC4803625, DOI: 10.1038/ni.3385.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisApoptosis Regulatory ProteinsAutoimmunityB-LymphocytesBcl-2-Like Protein 11Bone Marrow TransplantationCell Cycle ProteinsCell ProliferationDisease Models, AnimalHEK293 CellsHumansImmune ToleranceImmunoblottingLupus Erythematosus, SystemicMembrane ProteinsMiceMice, Inbred MRL lprMicroRNAsNuclear ProteinsProto-Oncogene ProteinsPTEN PhosphohydrolaseReverse Transcriptase Polymerase Chain ReactionSequence Analysis, RNA
2015
TNF receptor superfamily member 13b (TNFRSF13B) hemizygosity reveals transmembrane activator and CAML interactor haploinsufficiency at later stages of B-cell development
Romberg N, Virdee M, Chamberlain N, Oe T, Schickel JN, Perkins T, Cantaert T, Rachid R, Rosengren S, Palazzo R, Geha R, Cunningham-Rundles C, Meffre E. TNF receptor superfamily member 13b (TNFRSF13B) hemizygosity reveals transmembrane activator and CAML interactor haploinsufficiency at later stages of B-cell development. Journal Of Allergy And Clinical Immunology 2015, 136: 1315-1325. PMID: 26100089, PMCID: PMC4641026, DOI: 10.1016/j.jaci.2015.05.012.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedAged, 80 and overAntibody FormationAutoimmunityB-LymphocytesChildCommon Variable ImmunodeficiencyFemaleHaploinsufficiencyHemizygoteHumansImmunologic MemoryLymphocyte ActivationMaleMiddle AgedMutation, MissenseSmith-Magenis SyndromeT-Lymphocytes, RegulatoryTransmembrane Activator and CAML Interactor ProteinYoung AdultConceptsCommon variable immune deficiencyMemory B cellsB cell toleranceB cellsSmith-Magenis syndromeTACI expressionTNFRSF13B mutationsTransmembrane activatorB cell developmentTNF receptorRegulatory T cell functionPeripheral B cell toleranceAntibody-deficient patientsCentral B cell toleranceVariable immune deficiencyT cell functionAutoreactive B cellsNaive B cellsReactivity of antibodiesB cell activationMissense mutationsSingle B cellsAutoimmune featuresImmunologic featuresImmune deficiency
2014
Aberant expansion of CXCR5+ memory CD4 T cells in SLE patients (HUM7P.307)
Choi J, Kim S, Kang I, Craft J. Aberant expansion of CXCR5+ memory CD4 T cells in SLE patients (HUM7P.307). The Journal Of Immunology 2014, 192: 184.16-184.16. DOI: 10.4049/jimmunol.192.supp.184.16.Peer-Reviewed Original ResearchCD4 T cellsSLE patientsT cellsTfh cellsB cellsB collaborationB cell helper functionFollicular helper T cellsMemory CD4 T cellsMemory Tfh cellsTh17-like subsetsAnti-nuclear antibodiesHelper T cellsB cell responsesHuman lupus patientsSecondary lymphoid organsMemory B cellsAutoreactive B cellsSuch cellsDistinct Th1Autoantibody titersDisease activityLupus patientsIL-21Lymphoid organs
2013
CVID-associated TACI mutations affect autoreactive B cell selection and activation
Romberg N, Chamberlain N, Saadoun D, Gentile M, Kinnunen T, Ng YS, Virdee M, Menard L, Cantaert T, Morbach H, Rachid R, Martinez-Pomar N, Matamoros N, Geha R, Grimbacher B, Cerutti A, Cunningham-Rundles C, Meffre E. CVID-associated TACI mutations affect autoreactive B cell selection and activation. Journal Of Clinical Investigation 2013, 123: 4283-4293. PMID: 24051380, PMCID: PMC3786721, DOI: 10.1172/jci69854.Peer-Reviewed Original ResearchMeSH KeywordsAdultAntibodies, AntinuclearAutoantibodiesB-Cell Activating FactorB-LymphocytesCase-Control StudiesCell ProliferationCells, CulturedCentral ToleranceCommon Variable ImmunodeficiencyDNA-Binding ProteinsGene DosageHeterozygoteHumansLymphocyte ActivationMaleMiddle AgedMutationPeripheral ToleranceProto-Oncogene Proteins c-bcl-6T-Lymphocytes, Helper-InducerToll-Like Receptor 7Toll-Like Receptor 9Transmembrane Activator and CAML Interactor ProteinConceptsCommon variable immune deficiencyB cell activationAutoreactive B cellsTACI mutationsCell activationAntinuclear antibodiesCVID patientsB cellsFollicular helper cellsCentral B cell toleranceVariable immune deficiencyB cell responsivenessB-cell lymphoma 6B cell toleranceTumor necrosis factor receptorNecrosis factor receptorB cell selectionAutoimmune complicationsAutoimmune manifestationsPrimary diseaseAntibody deficiencyImmune toleranceHelper cellsTolerance checkpointsImmune deficiencySpecific peripheral B cell tolerance defects in patients with multiple sclerosis
Kinnunen T, Chamberlain N, Morbach H, Cantaert T, Lynch M, Preston-Hurlburt P, Herold KC, Hafler DA, O’Connor K, Meffre E. Specific peripheral B cell tolerance defects in patients with multiple sclerosis. Journal Of Clinical Investigation 2013, 123: 2737-2741. PMID: 23676463, PMCID: PMC3668812, DOI: 10.1172/jci68775.Peer-Reviewed Original ResearchConceptsB cell tolerance checkpointsB cell tolerance defectsMultiple sclerosisRheumatoid arthritisTolerance checkpointsB cellsPeripheral B cell tolerance checkpointsTolerance defectsAutoreactive B cell clonesMature naive B cellsType 1 diabetesAutoreactive B cellsB cell toleranceCentral nervous systemNaive B cellsB cell clonesB cell selectionEarly B cell developmentIPEX patientsMost patientsTreg functionHomeostatic proliferationAutoimmune diseasesPatientsHealthy individuals
2012
Accumulation of peripheral autoreactive B cells in the absence of functional human regulatory T cells
Kinnunen T, Chamberlain N, Morbach H, Choi J, Kim S, Craft J, Mayer L, Cancrini C, Passerini L, Bacchetta R, Ochs HD, Torgerson TR, Meffre E. Accumulation of peripheral autoreactive B cells in the absence of functional human regulatory T cells. Blood 2012, 121: 1595-1603. PMID: 23223361, PMCID: PMC3587322, DOI: 10.1182/blood-2012-09-457465.Peer-Reviewed Original ResearchConceptsB cell tolerancePeripheral B cell toleranceIPEX patientsRegulatory T cellsAutoreactive B cellsNaive B cellsB cellsT cellsTreg functionAutoreactive mature naive B cellsHuman B cell toleranceForkhead box protein 3 geneHuman regulatory T cellsMature naive B cellsTreg-like cellsCentral B cell toleranceSevere autoimmune disordersT-cell costimulatorTransitional B cellsRegulation of CD40LReactivity of antibodiesDefective Treg functionSingle B cellsPD-1Autoimmune disordersCaspase‐activated DNase is required for maintenance of tolerance to lupus nuclear autoantigens
Jog NR, Frisoni L, Shi Q, Monestier M, Hernandez S, Craft J, Prak ET, Caricchio R. Caspase‐activated DNase is required for maintenance of tolerance to lupus nuclear autoantigens. Arthritis & Rheumatism 2012, 64: 1247-1256. PMID: 22127758, PMCID: PMC3292632, DOI: 10.1002/art.33448.Peer-Reviewed Original ResearchConceptsSystemic lupus erythematosusAutoimmune responseMouse modelApoptotic cellsNuclear autoantigensDNA antibody titersLupus-prone miceAbsence of CADMaintenance of toleranceAutoreactive B cellsAnti-DNA antibodiesApoptotic modificationsLupus developmentGeneration of autoantigensAntinuclear antibodiesLupus erythematosusAntibody titersAutoimmune diseasesActive caspase-3Apoptotic bodiesB cellsMiceAutoantigensCAD deficiencyCaspase-3
2009
Differential Cytokine Production and Bystander Activation of Autoreactive B Cells in Response to CpG-A and CpG-B Oligonucleotides
Avalos AM, Latz E, Mousseau B, Christensen SR, Shlomchik MJ, Lund F, Marshak-Rothstein A. Differential Cytokine Production and Bystander Activation of Autoreactive B Cells in Response to CpG-A and CpG-B Oligonucleotides. The Journal Of Immunology 2009, 183: 6262-6268. PMID: 19864612, PMCID: PMC3426913, DOI: 10.4049/jimmunol.0901941.Peer-Reviewed Original ResearchTranslational Mini-Review Series on B Cell-Directed Therapies: B cell-directed therapy for autoimmune diseases
Hu C, Wong F, Wen L. Translational Mini-Review Series on B Cell-Directed Therapies: B cell-directed therapy for autoimmune diseases. Clinical & Experimental Immunology 2009, 157: 181-190. PMID: 19604257, PMCID: PMC2730843, DOI: 10.1111/j.1365-2249.2009.03977.x.Peer-Reviewed Original ResearchConceptsB cell-directed therapiesCell-directed therapiesAutoimmune diseasesB cellsT cellsRegulatory B cell subsetsOrgan-specific autoimmune diseasesTranslational Mini‐Review SeriesAmeliorate autoimmune diseaseRegulatory B cellsAnti-inflammatory cytokinesB cell subsetsAutoreactive B cellsMini‐Review SeriesProinflammatory cytokinesSpecific autoantigensCell subsetsTherapyDiseaseVicious cycleCytokinesCellsAutoantibodiesAutoantigensPathogenesisOR.39. Enumeration and Phenotype of Autoreactive B Cells in Pancreatic Draining Lymph Nodes from Type 1 Diabetes Subjects
Kent S, Bradshaw E, Han Q, Varadarajan N, Greer A, Love J, Hafler D. OR.39. Enumeration and Phenotype of Autoreactive B Cells in Pancreatic Draining Lymph Nodes from Type 1 Diabetes Subjects. Clinical Immunology 2009, 131: s19. DOI: 10.1016/j.clim.2009.03.051.Peer-Reviewed Original Research
This site is protected by hCaptcha and its Privacy Policy and Terms of Service apply