2023
T follicular helper cells in cancer, tertiary lymphoid structures, and beyond
Cui C, Craft J, Joshi N. T follicular helper cells in cancer, tertiary lymphoid structures, and beyond. Seminars In Immunology 2023, 69: 101797. PMID: 37343412, DOI: 10.1016/j.smim.2023.101797.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsTumor-associated tertiary lymphoid structuresFollicular helper cellsCD8 T cellsTertiary lymphoid structuresSecondary lymphoid organsT cellsHelper cellsLymphoid structuresImmune cellsB cellsCD4 T follicular helper cellsT Follicular Helper CellsTumor-infiltrating immune cellsCurrent immunotherapy regimensCheckpoint blockade immunotherapyCD4 T cellsImmune cell componentsLimited response rateFunctional immune cellsNovel therapeutic targetPotential therapeutic benefitT cell-B cell interactionsBlockade immunotherapyImmunotherapy regimensLymphoid organsAP-1–independent NFAT signaling maintains follicular T cell function in infection and autoimmunity
Seth A, Yokokura Y, Choi J, Shyer J, Vidyarthi A, Craft J. AP-1–independent NFAT signaling maintains follicular T cell function in infection and autoimmunity. Journal Of Experimental Medicine 2023, 220: e20211110. PMID: 36820828, PMCID: PMC9998660, DOI: 10.1084/jem.20211110.Peer-Reviewed Original ResearchConceptsTfh cellsT cellsFollicular helper T cellsLupus-prone miceT cell subsetsTfh cell developmentHelper T cellsHumoral immune responseT cell functionGerminal center B cellsT cell statesRenal injuryAutoantibody productionCell subsetsPrimary T cellsImmune responseB cellsPharmacologic inhibitionTherapeutic insightsCell functionGenetic disruptionNFATCell developmentCellsGene expressionThe ion transporter Na+-K+-ATPase enables pathological B cell survival in the kidney microenvironment of lupus nephritis
Chernova I, Song W, Steach H, Hafez O, Al Souz J, Chen P, Chandra N, Cantley L, Veselits M, Clark M, Craft J. The ion transporter Na+-K+-ATPase enables pathological B cell survival in the kidney microenvironment of lupus nephritis. Science Advances 2023, 9: eadf8156. PMID: 36724234, PMCID: PMC9891690, DOI: 10.1126/sciadv.adf8156.Peer-Reviewed Original ResearchMeSH KeywordsB-LymphocytesCell SurvivalHumansKidneyLupus NephritisSodiumSodium-Potassium-Exchanging ATPaseConceptsB cellsAutoimmune diseasesAmelioration of proteinuriaLupus nephritis biopsiesB cell infiltrationSodium-potassium adenosine triphosphataseB cell survivalPotassium adenosine triphosphataseLupus nephritisCell infiltrationKidney microenvironmentTissue injuryTherapeutic targetPharmacological inhibitionElevated sodium concentrationLupusHostile microenvironmentHigh expressionKidneySodium concentrationGenetic knockoutCell survivalDiseaseCellsAdenosine triphosphatase
2022
High-affinity, neutralizing antibodies to SARS-CoV-2 can be made without T follicular helper cells
Chen JS, Chow RD, Song E, Mao T, Israelow B, Kamath K, Bozekowski J, Haynes WA, Filler RB, Menasche BL, Wei J, Alfajaro MM, Song W, Peng L, Carter L, Weinstein JS, Gowthaman U, Chen S, Craft J, Shon JC, Iwasaki A, Wilen CB, Eisenbarth SC. High-affinity, neutralizing antibodies to SARS-CoV-2 can be made without T follicular helper cells. Science Immunology 2022, 7: eabl5652. PMID: 34914544, PMCID: PMC8977051, DOI: 10.1126/sciimmunol.abl5652.Peer-Reviewed Original ResearchConceptsSARS-CoV-2 infectionSARS-CoV-2Follicular helper cellsB cell responsesHelper cellsAntibody productionCell responsesSARS-CoV-2 vaccinationB-cell receptor sequencingSevere COVID-19Cell receptor sequencingIndependent antibodiesT cell-B cell interactionsViral inflammationAntiviral antibodiesImmunoglobulin class switchingVirus infectionGerminal centersViral infectionClonal repertoireInfectionAntibodiesClass switchingCOVID-19PatientsDevelopment of Tbet- and CD11c-expressing B cells in a viral infection requires T follicular helper cells outside of germinal centers
Song W, Antao OQ, Condiff E, Sanchez GM, Chernova I, Zembrzuski K, Steach H, Rubtsova K, Angeletti D, Lemenze A, Laidlaw BJ, Craft J, Weinstein JS. Development of Tbet- and CD11c-expressing B cells in a viral infection requires T follicular helper cells outside of germinal centers. Immunity 2022, 55: 290-307.e5. PMID: 35090581, PMCID: PMC8965751, DOI: 10.1016/j.immuni.2022.01.002.Peer-Reviewed Original ResearchConceptsFollicular helper cellsB cellsGC B cellsHelper cellsMemory subsetsRobust recall responsesB cell subsetsGerminal center formationB cell generationAcute infectionCell subsetsRecall responsesTh1 cellsProximal deliveryCD11cGerminal centersIntegrin LFA-1Viral infectionAntibody productionVLA-4Splenic retentionLFA-1TbetBCL6 expressionInfection
2021
Neoantigen-driven B cell and CD4 T follicular helper cell collaboration promotes anti-tumor CD8 T cell responses
Cui C, Wang J, Fagerberg E, Chen PM, Connolly KA, Damo M, Cheung JF, Mao T, Askari AS, Chen S, Fitzgerald B, Foster GG, Eisenbarth SC, Zhao H, Craft J, Joshi NS. Neoantigen-driven B cell and CD4 T follicular helper cell collaboration promotes anti-tumor CD8 T cell responses. Cell 2021, 184: 6101-6118.e13. PMID: 34852236, PMCID: PMC8671355, DOI: 10.1016/j.cell.2021.11.007.Peer-Reviewed Original ResearchConceptsCD8 TB cellsTfh cellsLung adenocarcinomaTfh-B cell interactionsTumor-specific B cellsFollicular helper cellsAnti-tumor immunityB cell signaturesCell effector functionsGerminal center formationGC B cellsCD4 THelper cellsTumor controlTumor neoantigensEffector functionsCell collaborationCell responsesCell signatureTumor cellsSignature correlatesNeoantigensCell functionCD4CD4+ T cells that help B cells – a proposal for uniform nomenclature
Eisenbarth SC, Baumjohann D, Craft J, Fazilleau N, Ma CS, Tangye SG, Vinuesa CG, Linterman MA. CD4+ T cells that help B cells – a proposal for uniform nomenclature. Trends In Immunology 2021, 42: 658-669. PMID: 34244056, PMCID: PMC8324560, DOI: 10.1016/j.it.2021.06.003.Peer-Reviewed Original ResearchMeSH KeywordsB-LymphocytesCell DifferentiationGerminal CenterImmunity, HumoralLymphocyte ActivationT-Lymphocytes, Helper-InducerConceptsTfh-like cellsB cellsT cellsFollicular helper cellsAntigen-primed B cellsSecondary lymphoid tissuesTranscription factor Bcl6B cell differentiationHelper cellsHumoral immunityLymphoid tissueChemokine receptorsAnatomical sitesImmune challengeDistinct subsetsDifferent isotypesCD4TfhCellular plasticityCellsCell differentiationUniform nomenclatureCytokinesImmunityAntibodiesT Follicular Regulatory Cells: Choreographers of Productive Germinal Center Responses
Lu Y, Craft J. T Follicular Regulatory Cells: Choreographers of Productive Germinal Center Responses. Frontiers In Immunology 2021, 12: 679909. PMID: 34177925, PMCID: PMC8222975, DOI: 10.3389/fimmu.2021.679909.Peer-Reviewed Original ResearchConceptsTfr cellsTreg cellsHumoral immunityGerminal centersAntigen-specific B cell responsesFollicular helper cellsFollicular regulatory (Tfr) cellsB cell folliclesRegulatory T cellsB cell autoreactivityB cell responsesGerminal center responseB cell toleranceVaccine design strategiesTranscription factor Bcl6Regulatory cellsHelper cellsImmune homeostasisProductive immunityT cellsViral infectionCenter responseCell responsesGC responseImmune challengeType I Interferon–Activated STAT4 Regulation of Follicular Helper T Cell–Dependent Cytokine and Immunoglobulin Production in Lupus
Dong X, Antao OQ, Song W, Sanchez GM, Zembrzuski K, Koumpouras F, Lemenze A, Craft J, Weinstein JS. Type I Interferon–Activated STAT4 Regulation of Follicular Helper T Cell–Dependent Cytokine and Immunoglobulin Production in Lupus. Arthritis & Rheumatology 2021, 73: 478-489. PMID: 33512094, PMCID: PMC7914134, DOI: 10.1002/art.41532.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnimalsAntibody FormationAutoantibodiesB-LymphocytesCase-Control StudiesCytokinesDisease Models, AnimalFemaleHumansImmunoglobulinsInterferon Type IInterferon-gammaInterleukinsLupus Erythematosus, SystemicMaleMice, Inbred MRL lprMiddle AgedRNA-SeqSTAT4 Transcription FactorT Follicular Helper CellsConceptsSystemic lupus erythematosusTfh-like cellsTfh cellsIL-21Human lupusDisease activityCytokine productionSTAT4 activationImmunoglobulin productionPathogenic B cell responsesCourse of lupusClinical disease activityT cell secretionLupus-prone miceHealthy control subjectsCourse of diseaseB cell responsesCytokine interleukin-21Potential therapeutic targetType I IFNB cell maturationSLE patientsPathogenic cytokinesLupus erythematosusInterleukin-21
2020
CD4+ follicular regulatory T cells optimize the influenza virus–specific B cell response
Lu Y, Jiang R, Freyn AW, Wang J, Strohmeier S, Lederer K, Locci M, Zhao H, Angeletti D, O’Connor K, Kleinstein SH, Nachbagauer R, Craft J. CD4+ follicular regulatory T cells optimize the influenza virus–specific B cell response. Journal Of Experimental Medicine 2020, 218: e20200547. PMID: 33326020, PMCID: PMC7748821, DOI: 10.1084/jem.20200547.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibody FormationAntigensB-LymphocytesCD4 AntigensDisease Models, AnimalEpitopesForkhead Transcription FactorsGerminal CenterHumansImmunityImmunologic MemoryInfluenza, HumanInfluenzavirus BIntegrasesMice, Inbred C57BLOrthomyxoviridae InfectionsReceptors, Antigen, B-CellSpecies SpecificityT-Lymphocytes, RegulatoryVaccinationConceptsB cell responsesGerminal center B cell responsesFollicular regulatory T cellsRegulatory T cellsTfr cellsCell responsesT cellsViral challengeHumoral memoryVirus-specific B cell responsesAntigen-specific B cell responsesFollicular helper T cellsHA stalk regionHelper T cellsInfluenza virus infectionGerminal center developmentAntibody responsePlasma cellsVirus infectionImmunization modelAntibody productionBCR repertoireInfluenza virusRepeated exposureInfluenza virus glycoproteins
2019
Impaired ATM activation in B cells is associated with bone resorption in rheumatoid arthritis
Mensah KA, Chen JW, Schickel JN, Isnardi I, Yamakawa N, Vega-Loza A, Anolik JH, Gatti RA, Gelfand EW, Montgomery RR, Horowitz MC, Craft JE, Meffre E. Impaired ATM activation in B cells is associated with bone resorption in rheumatoid arthritis. Science Translational Medicine 2019, 11 PMID: 31748230, PMCID: PMC7167286, DOI: 10.1126/scitranslmed.aaw4626.Peer-Reviewed Original ResearchConceptsRheumatoid arthritisB cellsHealthy donor controlsGroup of patientsHumanized mouse modelImmature B cellsGene segment usageErosive diseaseRA pathophysiologyBone erosionBone lossBone resorptionHigh prevalenceRANKL productionBone densityMouse modelReceptor activatorBone marrowPatientsDonor controlsCD21Segment usageArthritisElevated frequencyAtaxia telangiectasiaSpatial and functional heterogeneity of follicular helper T cells in autoimmunity
Seth A, Craft J. Spatial and functional heterogeneity of follicular helper T cells in autoimmunity. Current Opinion In Immunology 2019, 61: 1-9. PMID: 31374450, PMCID: PMC7255639, DOI: 10.1016/j.coi.2019.06.005.Peer-Reviewed Original ResearchConceptsHelper T cellsFollicular helper T cellsT cellsB cell helper T cellsTfh cell biologyB cell folliclesB cell helpT helper cellsNon-lymphoid tissuesAutoantibody-mediated autoimmunitySecondary lymphoidAutoimmune diseasesHelper cellsCell helpGerminal centersAnimal modelsB cell developmentHuman patientsPathogenic changesAutoimmunityProduction of affinityExtrafollicular spaceTherapeutic purposesFunctional heterogeneityCell developmentT follicular helper cell heterogeneity: Time, space, and function
Song W, Craft J. T follicular helper cell heterogeneity: Time, space, and function. Immunological Reviews 2019, 288: 85-96. PMID: 30874350, PMCID: PMC6422039, DOI: 10.1111/imr.12740.Peer-Reviewed Original Research
2018
Human Extrafollicular CD4+ Th Cells Help Memory B Cells Produce Igs.
Kim ST, Choi JY, Lainez B, Schulz VP, Karas DE, Baum ED, Setlur J, Gallagher PG, Craft J. Human Extrafollicular CD4+ Th Cells Help Memory B Cells Produce Igs. The Journal Of Immunology 2018, 201: 1359-1372. PMID: 30030323, PMCID: PMC6112860, DOI: 10.4049/jimmunol.1701217.Peer-Reviewed Original ResearchConceptsMemory B cellsHumoral recall responsesB cell folliclesT cell subsetsB cellsTfh cellsCell subsetsRecall responsesT cellsInhibitory receptor PD-1Follicular helper T cellsGerminal center B-cell maturationIL-21 secretionChemokine receptor expressionReceptor PD-1Helper T cellsT cell zonesPrimary immune responseChemokine receptor CXCR5Transcription factor Bcl6B cell maturationTonsillar CD4IL-10IL-21PD-1
2017
Interleukin-10 from CD4+ follicular regulatory T cells promotes the germinal center response
Laidlaw BJ, Lu Y, Amezquita RA, Weinstein JS, Vander Heiden JA, Gupta NT, Kleinstein SH, Kaech SM, Craft J. Interleukin-10 from CD4+ follicular regulatory T cells promotes the germinal center response. Science Immunology 2017, 2 PMID: 29054998, PMCID: PMC5846620, DOI: 10.1126/sciimmunol.aan4767.Peer-Reviewed Original ResearchConceptsFollicular regulatory T cellsRegulatory T cellsIL-10Lymphocytic choriomeningitis virusT cellsB cellsInterleukin-10GC responseCell-derived IL-10Follicular helper T cellsHelper T cellsB cell responsesGerminal center responseGerminal center developmentActivated B cellsBox protein 1GC B cellsAcute infectionCenter responseCell responsesImportant mediatorNuclear translocationGC reactionProtein 1Forkhead box protein 1Disruption of Pathogenic Cellular Networks by IL-21 Blockade Leads to Disease Amelioration in Murine Lupus.
Choi JY, Seth A, Kashgarian M, Terrillon S, Fung E, Huang L, Wang LC, Craft J. Disruption of Pathogenic Cellular Networks by IL-21 Blockade Leads to Disease Amelioration in Murine Lupus. The Journal Of Immunology 2017, 198: 2578-2588. PMID: 28219887, PMCID: PMC5360548, DOI: 10.4049/jimmunol.1601687.Peer-Reviewed Original ResearchConceptsIL-21Systemic lupus erythematosusMurine lupusTfh cellsLupus erythematosusDisease ameliorationGerminal center B cell responsesTfh-B cell interactionsGC responseFollicular Th cellsIL-21 blockadeLupus-prone B6Progression of glomerulonephritisCell-derived cytokinesB cell responsesMemory B cell developmentPotential therapeutic strategyB cell proliferationB cell maturationGC B cellsOverall survivalOrgan injuryAutoantibody productionLatter cytokineTh cells
2016
TFH cells progressively differentiate to regulate the germinal center response
Weinstein JS, Herman EI, Lainez B, Licona-Limón P, Esplugues E, Flavell R, Craft J. TFH cells progressively differentiate to regulate the germinal center response. Nature Immunology 2016, 17: 1197-1205. PMID: 27573866, PMCID: PMC5030190, DOI: 10.1038/ni.3554.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibody AffinityB-LymphocytesCD4 AntigensCell CommunicationCell DifferentiationCells, CulturedGene Expression RegulationGerminal CenterHumansInterleukin-4InterleukinsMiceMice, Inbred C57BLMice, Mutant StrainsMutationNippostrongylusPositive Regulatory Domain I-Binding Factor 1Strongylida InfectionsT-Lymphocytes, Helper-InducerTranscription Factors
2015
The transforming growth factor beta signaling pathway is critical for the formation of CD4 T follicular helper cells and isotype-switched antibody responses in the lung mucosa
Marshall HD, Ray JP, Laidlaw BJ, Zhang N, Gawande D, Staron MM, Craft J, Kaech SM. The transforming growth factor beta signaling pathway is critical for the formation of CD4 T follicular helper cells and isotype-switched antibody responses in the lung mucosa. ELife 2015, 4: e04851. PMID: 25569154, PMCID: PMC4337607, DOI: 10.7554/elife.04851.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibody FormationB-LymphocytesCell DifferentiationGene Expression ProfilingGerminal CenterImmunoglobulin Class SwitchingLungMiceMucous MembraneOrthomyxoviridaeOrthomyxoviridae InfectionsSignal TransductionSpecies SpecificityT-Lymphocytes, Helper-InducerTOR Serine-Threonine KinasesTransforming Growth Factor betaConceptsCD4 T cellsFollicular helper cellsTfh cellsAntibody responseT cellsHelper cellsViral infectionCD4 T follicular helper cellsVirus-specific CD4 T cellsIL-2 receptor α chainT Follicular Helper CellsRespiratory viral infectionsAcute viral infectionGrowth factor betaGerminal center reactionReceptor α chainInhibition of mTORIL-2 signalingLung mucosaTfh differentiationHumoral responseRapamycin (mTOR) activationTGF-βRFactor betaCenter reaction
2014
Dynamic signaling by T follicular helper cells during germinal center B cell selection
Shulman Z, Gitlin AD, Weinstein JS, Lainez B, Esplugues E, Flavell RA, Craft JE, Nussenzweig MC. Dynamic signaling by T follicular helper cells during germinal center B cell selection. Science 2014, 345: 1058-1062. PMID: 25170154, PMCID: PMC4519234, DOI: 10.1126/science.1257861.Peer-Reviewed Original ResearchConceptsFollicular helper cellsB cellsGC B cellsHelper cellsGerminal centersAntibody-producing B cellsCytokine interleukin-4B cell selectionGerminal center B cell selectionInterleukin-4Transient elevationMajor histocompatibilitySustained increaseFree calciumClonal expansionCognate peptideIntravital imagingCell migrationCellsIntracellularCell selectionHigh levelsHistocompatibilityB Cells in T Follicular Helper Cell Development and Function: Separable Roles in Delivery of ICOS Ligand and Antigen
Weinstein JS, Bertino SA, Hernandez SG, Poholek AC, Teplitzky TB, Nowyhed HN, Craft J. B Cells in T Follicular Helper Cell Development and Function: Separable Roles in Delivery of ICOS Ligand and Antigen. The Journal Of Immunology 2014, 192: 3166-3179. PMID: 24610013, PMCID: PMC3991608, DOI: 10.4049/jimmunol.1302617.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigensAntigens, CD19B-LymphocytesCell ProliferationDNA-Binding ProteinsFlow CytometryInducible T-Cell Co-Stimulator LigandMiceMice, Inbred C57BLMice, KnockoutMice, TransgenicMicroscopy, ConfocalNitrophenolsOvalbuminPhenylacetatesProto-Oncogene Proteins c-bcl-6Reverse Transcriptase Polymerase Chain ReactionT-LymphocytesT-Lymphocytes, Helper-InducerConceptsCognate B cellsTfh cell developmentB cellsICOS ligandFollicular Th cell developmentCell developmentNoncognate B cellsFollicular helper cell developmentTfh cell differentiationAg-specific B cellsICOS-L expressionB cell expressionTh cell developmentGerminal center differentiationICOS blockadeTfh cellsAg deliverySystemic autoimmunityCell expressionCell maturationICOSCellsDeliveryCell differentiationCells display