2024
Tlr9 deficiency in B cells leads to obesity by promoting inflammation and gut dysbiosis
Wang P, Yang X, Zhang L, Sha S, Huang J, Peng J, Gu J, Pearson J, Hu Y, Zhao H, Wong F, Wang Q, Wen L. Tlr9 deficiency in B cells leads to obesity by promoting inflammation and gut dysbiosis. Nature Communications 2024, 15: 4232. PMID: 38762479, PMCID: PMC11102548, DOI: 10.1038/s41467-024-48611-8.Peer-Reviewed Original ResearchConceptsToll-like receptor 9Gut microbiotaGut microbial communityTransferred to germ-free miceB cellsGerm-free miceTLR9 deficiencyKO miceGene sequencesGerminal center B cellsMicrobial communitiesMarginal zone B cellsGut dysbiosisFollicular helper cellsSelf-DNAMetabolic homeostasisAssociated with increased frequencyPro-inflammatory stateFat tissue inflammationGutHigh-fat dietMicrobiotaHelper cellsT cellsControl mice
2021
Toll-like receptor 7 deficiency suppresses type 1 diabetes development by modulating B-cell differentiation and function
Huang J, Peng J, Pearson JA, Efthimiou G, Hu Y, Tai N, Xing Y, Zhang L, Gu J, Jiang J, Zhao H, Zhou Z, Wong FS, Wen L. Toll-like receptor 7 deficiency suppresses type 1 diabetes development by modulating B-cell differentiation and function. Cellular & Molecular Immunology 2021, 18: 328-338. PMID: 33432061, PMCID: PMC8027372, DOI: 10.1038/s41423-020-00590-8.Peer-Reviewed Original ResearchConceptsType 1 diabetes developmentToll-like receptorsType 1 diabetesDiabetes developmentB cellsTLR7 deficiencyNOD miceB cell differentiationT cellsClassical MHC class I moleculesHuman type 1 diabetesImmunodeficient NOD miceNOD B cellsDiabetogenic T cellsAntigen-presenting functionNonobese diabetic (NOD) miceT cell responsesB cell functionMHC class I moleculesPattern recognition receptorsT cell activationPathogen molecular patternsClass I moleculesDiabetogenic CD4Cytotoxic CD8
2020
Insulin-Reactive T Cells Convert Diabetogenic Insulin-Reactive VH125 B Cells Into Tolerogenic Cells by Reducing Germinal Center T:B Cell Interactions in NOD Mice
Pearson JA, Li Y, Majewska-Szczepanik M, Guo J, Zhang L, Liu Y, Wong FS, Wen L. Insulin-Reactive T Cells Convert Diabetogenic Insulin-Reactive VH125 B Cells Into Tolerogenic Cells by Reducing Germinal Center T:B Cell Interactions in NOD Mice. Frontiers In Immunology 2020, 11: 585886. PMID: 33262765, PMCID: PMC7688534, DOI: 10.3389/fimmu.2020.585886.Peer-Reviewed Original ResearchConceptsB cell interactionsTransgenic NOD miceNOD miceT cellsB cellsT1D developmentAntigen-specific regulatory T cellsInsulin-reactive B cellsInsulin-reactive T cellsNon-obese diabetic (NOD) miceGerminal center TInsulin-reactive CD4Non-germinal centerCell interactionsCostimulatory molecule expressionRegulatory T cellsType 1 diabetesGC B cellsTolerogenic cellsAdoptive transferDiabetic miceTGFβ secretionMolecule expressionIgG isotypeKey autoantigenAltered Systemic and Intestinal IgA Immune Responses in Individuals With Type 1 Diabetes
Huang J, Huang G, Li X, Hu F, Xie Z, Xiao Y, Luo S, Chao C, Guo K, Wong FS, Zhou Z, Wen L. Altered Systemic and Intestinal IgA Immune Responses in Individuals With Type 1 Diabetes. The Journal Of Clinical Endocrinology & Metabolism 2020, 105: dgaa590. PMID: 32860693, PMCID: PMC7549925, DOI: 10.1210/clinem/dgaa590.Peer-Reviewed Original ResearchConceptsIgA-bound bacteriaType 1 diabetesHealthy control individualsIgA immune responseControl individualsIgA immunityAutoantibody titersIgA concentrationsImmune responseType 1 diabetes patientsΒ-cell autoimmunityLonger disease durationSerum IgA concentrationNovel therapeutic targetEnzyme-linked immunosorbentDisease durationIgA levelsDiabetes patientsDiabetes displayGut homeostasisBlood samplesOral cavityTherapeutic targetDiabetesHost immunity
2013
Combination Treatment With Anti-CD20 and Oral Anti-CD3 Prevents and Reverses Autoimmune Diabetes
Hu C, Ding H, Zhang X, Wong FS, Wen L. Combination Treatment With Anti-CD20 and Oral Anti-CD3 Prevents and Reverses Autoimmune Diabetes. Diabetes 2013, 62: 2849-2858. PMID: 23447122, PMCID: PMC3717853, DOI: 10.2337/db12-1175.Peer-Reviewed Original ResearchConceptsT cellsNOD miceB cellsT cell-mediated autoimmune diseaseB cell-directed therapiesB cell depletion therapyCell-mediated autoimmune diseaseDiabetic NOD miceTransgenic NOD miceRegulatory T cellsCD4 T cellsCell-directed therapiesAnti-CD3 treatmentType 1 diabetesCD20 monotherapyImportant preclinical evidenceDepletion therapyT1D developmentDendritic cellsIL-10Preclinical evidenceFurther mechanistic studiesAutoimmune diseasesAnti-CD20Suppressive function
2012
Type 1 diabetes therapy beyond T cell targeting: monocytes, B cells, and innate lymphocytes.
Wong F, Wen L. Type 1 diabetes therapy beyond T cell targeting: monocytes, B cells, and innate lymphocytes. The Review Of Diabetic Studies 2012, 9: 289-304. PMID: 23804267, PMCID: PMC3740697, DOI: 10.1900/rds.2012.9.289.Peer-Reviewed Original ResearchConceptsInnate lymphocytesB cellsT cell targetingNatural killer cellsRecent clinical trialsPathogenesis of T1DType 1 diabetesType 1 diabetes therapyKiller cellsSpecific therapyClinical trialsT cellsDisease processDiabetes therapyMultifactorial diseaseCell pathwaysMultiple cell typesDiabetesT1DLymphocytesTherapyMonocytesDiseaseSuitable targetCell typesThe Role of Gr1+ Cells after Anti-CD20 Treatment in Type 1 Diabetes in Nonobese Diabetic Mice
Hu C, Du W, Zhang X, Wong FS, Wen L. The Role of Gr1+ Cells after Anti-CD20 Treatment in Type 1 Diabetes in Nonobese Diabetic Mice. The Journal Of Immunology 2012, 188: 294-301. PMID: 22140261, PMCID: PMC4361178, DOI: 10.4049/jimmunol.1101590.Peer-Reviewed Original ResearchConceptsType 1 diabetesT cell functionNOD miceCD8 T cell functionRegulatory T cell differentiationAnti-CD20 treatmentPancreatic islet autoimmunityB-cell depletionCell contact-dependent mannerNonobese diabetic (NOD) miceCell functionT cell differentiationContact-dependent mannerDiabetogenic CD4Islet autoimmunityNovel immunotherapiesIL-10Immune toleranceDiabetic miceAutoimmune diseasesCell depletionImmunoregulatory functionsDiabetesMiceDependent manner
2010
To B or not to B—pathogenic and regulatory B cells in autoimmune diabetes
Wong F, Hu C, Xiang Y, Wen L. To B or not to B—pathogenic and regulatory B cells in autoimmune diabetes. Current Opinion In Immunology 2010, 22: 723-731. PMID: 21050736, DOI: 10.1016/j.coi.2010.10.002.Peer-Reviewed Original Research
2009
Translational 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 cycleCytokinesCellsAutoantibodiesAutoantigensPathogenesis
2008
Differences in immune recognition of cytochrome P4502D6 by liver kidney microsomal (LKM) antibody in autoimmune hepatitis and chronic hepatitis C virus infection
MA Y, PEAKMAN M, LOBO-YEO A, WEN L, LENZI M, GÄKEN J, FARZANEH F, MIELI-VERGANI G, BIANCHI F, VERGANI D. Differences in immune recognition of cytochrome P4502D6 by liver kidney microsomal (LKM) antibody in autoimmune hepatitis and chronic hepatitis C virus infection. Clinical & Experimental Immunology 2008, 97: 94-99. PMID: 8033426, PMCID: PMC1534799, DOI: 10.1111/j.1365-2249.1994.tb06585.x.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedAntibody SpecificityAutoantibodiesAutoantigensAutoimmune DiseasesB-LymphocytesChildChild, PreschoolCytochrome P-450 CYP2D6Cytochrome P-450 Enzyme SystemFemaleHepatitisHepatitis CHepatitis, ChronicHumansInfantMaleMiddle AgedMixed Function OxygenasesRecombinant Fusion ProteinsConceptsChronic hepatitis C virus (HCV) infectionHepatitis C virus infectionLKM-1 antibodiesAutoimmune hepatitisC virus infectionLKM-1HCV infectionVirus infectionCytochrome P4502D6Liver kidney microsomal antibodiesClassical autoimmune hepatitisKidney microsomal antibodyChronic HCV infectionLymphoblastoid B cell linesMicrosomal antibodiesPositive patientsLiver diseaseB cell linesHCVPatientsImmune recognitionMolecular mimicryRecombinant CYP2D6Western blotCYP2D6
2007
Treatment with CD20-specific antibody prevents and reverses autoimmune diabetes in mice
Hu CY, Rodriguez-Pinto D, Du W, Ahuja A, Henegariu O, Wong FS, Shlomchik MJ, Wen L. Treatment with CD20-specific antibody prevents and reverses autoimmune diabetes in mice. Journal Of Clinical Investigation 2007, 117: 3857-3867. PMID: 18060033, PMCID: PMC2096456, DOI: 10.1172/jci32405.Peer-Reviewed Original ResearchConceptsB-cell depletionCell depletionB cellsNOD miceTherapeutic B cell depletionTransgenic NOD miceRegulatory B cellsLong-term remissionExpansion of TregsOnset of diabetesType 1 diabetesReverse diabetesClinical efficacyDiabetic miceAutoimmune diseasesFrank hyperglycemiaAntigen presentationT cellsHuman CD20DiabetesTherapeutic actionMiceClinical hyperglycemiaDiseasePotential mechanisms
2004
Investigation of the Role of B-Cells in Type 1 Diabetes in the NOD Mouse
Wong FS, Wen L, Tang M, Ramanathan M, Visintin I, Daugherty J, Hannum LG, Janeway CA, Shlomchik MJ. Investigation of the Role of B-Cells in Type 1 Diabetes in the NOD Mouse. Diabetes 2004, 53: 2581-2587. PMID: 15448087, DOI: 10.2337/diabetes.53.10.2581.Peer-Reviewed Original ResearchConceptsB cell-deficient miceAntigen-presenting functionType 1 diabetesB cellsNOD miceNormal NOD miceIncidence of diabetesDevelopment of diabetesT cell repertoireB cell repertoireAntigen presentationDiabetesAntibody productionMiceImmunoglobulin transgenesReduced abilityCell surfaceInsulitisAutoantibodiesIncidenceImmunoglobulinAntibodies
1998
Primary gamma delta cell clones can be defined phenotypically and functionally as Th1/Th2 cells and illustrate the association of CD4 with Th2 differentiation.
Wen L, Barber D, Pao W, Wong F, Owen M, Hayday A. Primary gamma delta cell clones can be defined phenotypically and functionally as Th1/Th2 cells and illustrate the association of CD4 with Th2 differentiation. The Journal Of Immunology 1998, 160: 1965-74. PMID: 9469460, DOI: 10.4049/jimmunol.160.4.1965.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsApoptosisB-LymphocytesCD4 AntigensCell DifferentiationCells, CulturedClone CellsCytokinesFas Ligand ProteinFas ReceptorGene ExpressionImmunoglobulin Class SwitchingImmunoglobulin IsotypesImmunophenotypingMembrane GlycoproteinsMiceMice, KnockoutMice, SCIDMolecular Sequence DataReceptors, Antigen, T-Cell, alpha-betaTh1 CellsTh2 CellsConceptsAlpha beta T cellsBeta T cellsGamma delta cellsT cellsCell clonesTh1/Th2 cellsGamma delta T cellsCD8 alpha betaDelta cellsDelta T cellsDivision of CD4Association of CD4Autoimmune diseasesCytokine expressionImmunoregulatory roleTh2 phenotypeTh2 subsetsTh2 cellsAntigen presentationCD4 expressionTh2 differentiationCD4Clonal levelAlpha betaStrong association
1996
γδ T cell help of B cells is induced by repeated parasitic infection, in the absence of other T cells
Pao W, Wen L, Smith A, Gulbranson-Judge A, Zheng B, Kelsoe G, MacLennan I, Owen M, Hayday A. γδ T cell help of B cells is induced by repeated parasitic infection, in the absence of other T cells. Current Biology 1996, 6: 1317-1325. PMID: 8939571, DOI: 10.1016/s0960-9822(02)70718-5.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, AntinuclearAntibodies, ProtozoanB-LymphocytesCD4 AntigensCoccidiosisEimeriaGene Rearrangement, gamma-Chain T-Cell Antigen ReceptorGerminal CenterImmunity, CellularImmunoglobulin GMiceMice, Mutant StrainsReceptors, Antigen, T-Cell, gamma-deltaT-Lymphocytes, Helper-InducerConceptsGamma delta T cellsDelta T cellsT cell-B cell collaborationT cell helpT cell-deficient miceCell-deficient miceGamma delta cellsT cellsCell helpB cellsGerminal centersParasitic infectionsCell collaborationAlpha beta T cellsBeta T cellsT cell deficiencyDelta cellsDevelopment of autoimmunityAntibody levelsMycobacterial antigensCell deficiencyImmune responseAnatomical focusImmune systemAntibody specificity
1994
Immunoglobulin synthesis and generalized autoimmunity in mice congenitally deficient in αβ(+) T cells
Wen L, Roberts S, Viney J, Wong F, Mallick C, Findly R, Peng Q, Craft J, Owen M, Mayday A. Immunoglobulin synthesis and generalized autoimmunity in mice congenitally deficient in αβ(+) T cells. Nature 1994, 369: 654-658. PMID: 8208291, DOI: 10.1038/369654a0.Peer-Reviewed Original ResearchConceptsΑβ T cellsT cellsT cell antigen receptorB cell-T cell interactionsHelp of CD4Provision of cytokinesB cell hyperactivitySystemic lupus erythematosusCognate B cell-T cell interactionT cell functionGeneralized autoimmunityLupus erythematosusTransplant rejectionIgE secretionImmunoglobulin synthesisB cellsIgG3 secretionAntigen receptorCD4AutoimmunityMiceSecretionAntibodiesCellsErythematosus
1991
Transient T and B cell activation after neonatal induction of tolerance to MHC class II or Mls alloantigens.
Schurmans S, Brighouse G, Kramer G, Wen L, Izui S, Merino J, Lambert P. Transient T and B cell activation after neonatal induction of tolerance to MHC class II or Mls alloantigens. The Journal Of Immunology 1991, 146: 2152-60. PMID: 1672344, DOI: 10.4049/jimmunol.146.7.2152.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnimals, NewbornAntibodies, AntinuclearAntigen-Antibody ComplexAntigens, Differentiation, T-LymphocyteAntigens, SurfaceAutoimmune DiseasesB-LymphocytesCD4-Positive T-LymphocytesCD8 AntigensHistocompatibility Antigens Class IHistocompatibility Antigens Class IIHypergammaglobulinemiaImmune ToleranceInterferon-gammaInterleukin-4Lymphocyte ActivationMajor Histocompatibility ComplexMiceMice, Inbred StrainsMinor Lymphocyte Stimulatory AntigensPlatelet CountReceptors, Antigen, T-CellThymus GlandT-LymphocytesConceptsMHC class IIB cell activationCell activationSpleen cellsClass IIAlloreactive CD4Neonatal injectionInjected miceT cellsF1 cellsTransient B cell activationIa AgLupus-like autoimmune syndromeSpecific toleranceClass IMajor histocompatibility complex class IFeatures of autoimmunityF1 spleen cellsTh cell responsesHistocompatibility complex class ICell-injected miceInduction of toleranceEarly postnatal periodComplex class IMHC class I
1988
Quantitative Analysis of Precursors Frequency of Rheumatoid Factor (RF) Producing Human B Cells
Vischer T, Werner-Favre C, Wen L, Zubler R. Quantitative Analysis of Precursors Frequency of Rheumatoid Factor (RF) Producing Human B Cells. Scandinavian Journal Of Rheumatology 1988, 17: 123-126. PMID: 3266359, DOI: 10.3109/03009748809096752.Peer-Reviewed Original Research
1987
Theoretical and Practical Aspects of B‐Cell Activation: Murine and Human Systems
Zubler R, Werner‐Favre C, Wen L, Sebcita K, Straub C. Theoretical and Practical Aspects of B‐Cell Activation: Murine and Human Systems. Immunological Reviews 1987, 99: 281-299. PMID: 2960608, DOI: 10.1111/j.1600-065x.1987.tb01181.x.Peer-Reviewed Original ResearchLimiting dilution assay for human B cells based on their activation by mutant EL4 thymoma cells: total and anti‐malaria responder B cell frequencies
Wen L, Hanvanich M, Werner‐Favre C, Brouwers N, Perrin L, Zubler R. Limiting dilution assay for human B cells based on their activation by mutant EL4 thymoma cells: total and anti‐malaria responder B cell frequencies. European Journal Of Immunology 1987, 17: 887-892. PMID: 3297736, DOI: 10.1002/eji.1830170624.Peer-Reviewed Original ResearchConceptsAntibody-secreting cellsB cellsPeripheral blood B cellsHuman B cell responsesB cell frequenciesB cell responsesBlood B cellsB cell activationHuman T cellsHuman B cellsMalaria infectionPeripheral bloodBlood donorsT cellsEL4 thymoma cellsMacrophage supernatantsControl groupCell frequencyCell activationCell responsesSpecificity repertoireInfectious diseasesClonal levelCulture systemMean amount