2025
Extrafollicular and Other Non‐Germinal Center B Cell Responses: An Evolutionary Perspective
Flowers E, Siniscalco E, Eisenbarth S. Extrafollicular and Other Non‐Germinal Center B Cell Responses: An Evolutionary Perspective. Immunological Reviews 2025, 334: e70060. PMID: 40938272, DOI: 10.1111/imr.70060.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsB-LymphocytesBiological EvolutionGerminal CenterHumansImmunity, HumoralLymphocyte ActivationConceptsGerminal centersHumoral immunityMultiple generaImmunological foundationsVertebrate evolutionAdjacent T cellsB cell responsesB cell proliferationB-cell regionsGC-independent pathwayMammalsT cellsHumoral protectionMechanisms of humoral immunityGC responsePathwayProtective antibodiesOrgan sitesAntibody responseAntigen depositionAntibodiesGenusTissue‐Resident T Cells That Promote Humoral Immunity: Emerging From the Shadow of T Follicular Helper Cells
Chen S, Craft J. Tissue‐Resident T Cells That Promote Humoral Immunity: Emerging From the Shadow of T Follicular Helper Cells. Immunological Reviews 2025, 334: e70056. PMID: 40890948, PMCID: PMC12402542, DOI: 10.1111/imr.70056.Peer-Reviewed Original ResearchConceptsB cell folliclesB cell maturationHelper cellsT cellsB cellsB-cell follicles of secondary lymphoid organsFollicles of secondary lymphoid organsT follicular helper (Tfh) cellsHumoral immunityRegulate B-cell maturationTissue-resident T cellsT Follicular Helper CellsFunction of T cellsAntibody-producing plasma cellsB cell helpDevelopment of humoral immunitySecondary lymphoid organsLocal humoral responseNon-lymphoid tissuesHumoral immune responseImmune challengeSystemic immune protectionCentral nervous systemTfh cellsImmunoglobulin class switch recombinationHumoral determinants of checkpoint immunotherapy
Dai Y, Aizenbud L, Qin K, Austin M, Jaycox J, Cunningham J, Wang E, Zhang L, Fischer S, Carroll S, van Aggelen H, Kluger Y, Herold K, Furchtgott L, Kluger H, Ring A. Humoral determinants of checkpoint immunotherapy. Nature 2025, 644: 527-536. PMID: 40702172, DOI: 10.1038/s41586-025-09188-4.Peer-Reviewed Original ResearchConceptsCheckpoint immunotherapyPreclinical mouse tumor modelsImmune-related adverse eventsIFN-IAntibody-mediated humoral immunityResponse to therapyTumor surface proteinMouse tumor modelsType I interferonIndividual autoantibodiesAutoantibody signaturesAdverse eventsAutoantibody responseCellular immunityTumor modelHumoral immunityAutoantibodiesOdds ratioIL-6Healthy control participantsHealthy individualsControl individualsI interferonPatientsGrowth factorImpact of memory T cells on SARS-CoV-2 vaccine response in hematopoietic stem cell transplant
VanOudenhove J, Liu Y, Nelakanti R, Kim D, Busarello E, Ovalle N, Qi Z, Mamillapalli P, Siddon A, Bai Z, Axtmayer A, Corso C, Kothari S, Foss F, Isufi I, Tebaldi T, Gowda L, Fan R, Seropian S, Halene S. Impact of memory T cells on SARS-CoV-2 vaccine response in hematopoietic stem cell transplant. PLOS ONE 2025, 20: e0320744. PMID: 40294012, PMCID: PMC12036906, DOI: 10.1371/journal.pone.0320744.Peer-Reviewed Original ResearchConceptsHematopoietic stem cell transplantationMemory T cellsStem cell transplantationCell transplantationT cellsSARS-CoV-2Hematopoietic stem cell transplant recipientsAntigen-specific T-cell activationSARS-CoV-2 mRNA vaccinesSARS-CoV-2 vaccine responsesSevere diseaseAnti-spike IgGT cell activationAdaptive immune responsesRobust antibody responsesPost-vaccination responseSARS-CoV-2 infectionMRNA vaccine seriesSingle-cell RNAMyeloablative chemotherapyCellular responsesImmune profileVaccine responseCOVID-19 infectionMRNA vaccinesWild Florida mottled ducks demonstrate strong heterogeneity in their humoral innate immune response.
Ayala A, Cheng M, Hellinger T, McBride K, Webb J, Fanning A, Snyder P, Ferragamo M, Garcia S, Sterner N, Bischoff K, Almagro-Moreno S, Ogbunugafor C. Wild Florida mottled ducks demonstrate strong heterogeneity in their humoral innate immune response. PLOS ONE 2025, 20: e0312653. PMID: 40096078, PMCID: PMC11913296, DOI: 10.1371/journal.pone.0312653.Peer-Reviewed Original ResearchConceptsFlorida mottled ducksAmerican Type Culture CollectionMottled ducksHumoral innate immune responseType Culture CollectionInnate immune responseVibrio sppEndemic subspeciesHabitat conversionInnate immune systemEco-immunologyCulture CollectionE. coliAnas platyrhynchosSubspeciesPeninsular FloridaConservation needsEffects of climate changeEcological covariatesHumoral innate immune systemBactericidal assayDucksResponse to agingWaterborne pathogensPathogens
2024
Booster COVID-19 mRNA vaccination ameliorates impaired B-cell but not T-cell responses in older adults
Kometani K, Yorimitsu T, Jo N, Yamaguchi E, Kikuchi O, Fukahori M, Sawada T, Tsujimoto Y, Sunami A, Li M, Ito T, Pretemer Y, Gao Y, Hidaka Y, Yamamoto M, Kaku N, Nakagama Y, Kido Y, Grifoni A, Sette A, Nagao M, Morita S, Nakajima T, Muto M, Hamazaki Y. Booster COVID-19 mRNA vaccination ameliorates impaired B-cell but not T-cell responses in older adults. Frontiers In Immunology 2024, 15: 1455334. PMID: 39717779, PMCID: PMC11663736, DOI: 10.3389/fimmu.2024.1455334.Peer-Reviewed Original ResearchMeSH KeywordsAdultAge FactorsAgedAged, 80 and overAntibodies, ViralB-LymphocytesCD8-Positive T-LymphocytesCOVID-19COVID-19 VaccinesFemaleHumansImmunity, HumoralImmunization, SecondaryImmunoglobulin GImmunologic MemoryMaleMemory B CellsMiddle AgedmRNA VaccinesSARS-CoV-2Spike Glycoprotein, CoronavirusYoung AdultConceptsB cell responsesT cell responsesB cellsT cellsBooster vaccinationT cell-mediated cellular immunityCD8<sup>+</sup> T cell responsesCytotoxic CD8<sup>+</sup> T cell responsesReduced PD-1 expressionMemory T cell activationMemory B cell responsesCOVID-19 mRNA booster vaccinationPD-1 expressionCOVID-19 mRNA vaccinesMemory T cellsImpaired humoral immunityImpaired B cellYoung adultsT cell activationMRNA booster vaccinationEnhanced IgG responseSpike-specificCellular immunityMRNA vaccinesAge-associated differencesTwo-dose priming immunization amplifies humoral immunity by synchronizing vaccine delivery with the germinal center response
Bhagchandani S, Yang L, Lam J, Maiorino L, Ben-Akiva E, Rodrigues K, Romanov A, Suh H, Aung A, Wu S, Wadhera A, Chakraborty A, Irvine D. Two-dose priming immunization amplifies humoral immunity by synchronizing vaccine delivery with the germinal center response. Science Immunology 2024, 9: eadl3755-eadl3755. PMID: 39303017, PMCID: PMC11492009, DOI: 10.1126/sciimmunol.adl3755.Peer-Reviewed Original ResearchMeSH KeywordsAIDS VaccinesAnimalsB-LymphocytesFemaleGerminal CenterImmunity, HumoralMiceMice, Inbred C57BLVaccines, SubunitConceptsDendritic cellsGerminal centersHumoral immunityAntigen-specific germinal centerGerminal center responseSubunit vaccineFollicular dendritic cellsPrimary immune responseIncreased T<sub>rDose 7 daysPrime immunizationGC responseImmune responseVaccine deliveryCenter responseAdministered vaccinesImmunityVaccineRegimensAdjuvant vaccineDoseCellsHIVResponseBolusSUMO-specific protease 1 regulates germinal center B cell response through deSUMOylation of PAX5
Qi J, Yan L, Sun J, Huang C, Su B, Cheng J, Shen L. SUMO-specific protease 1 regulates germinal center B cell response through deSUMOylation of PAX5. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 121: e2314619121. PMID: 38776375, PMCID: PMC11145296, DOI: 10.1073/pnas.2314619121.Peer-Reviewed Original ResearchConceptsPaired box protein 5GC B cellsSUMO-specific protease 1Activation-induced cytidine deaminaseProtein SUMOylationClass switch recombinationProtein stabilityB cellsProtease 1B cell responsesProtein 5Cytidine deaminaseSENP1Up-regulatedGC B cell responsesSomatic hypermutationSUMOylationDeSUMOylationGerminal centersHigher affinityProduction of class-switched antibodiesGerminal center B cell responsesGC reactionMemory B cellsClass-switched antibodies
2023
Diverging humoral and cellular immune responses due to Omicron—a national study from the Faroe Islands
Petersen M, Pérez-Alós L, Kongsstovu S, Eliasen E, Hansen C, Larsen S, Hansen J, Bayarri-Olmos R, Fjallsbak J, Weihe P, Garred P. Diverging humoral and cellular immune responses due to Omicron—a national study from the Faroe Islands. Microbiology Spectrum 2023, 11: e00865-23. PMID: 37909772, PMCID: PMC10714973, DOI: 10.1128/spectrum.00865-23.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, NeutralizingAntibodies, ViralDenmarkHumansImmune EvasionImmunity, CellularImmunity, HumoralVaccinationConceptsT cell responsesOmicron infectionHumoral responseUnvaccinated individualsImmune responseRobust T cell responsesSARS-CoV-2 Omicron variantPositive T-cell responsesDetectable humoral responseLow humoral responseLower humoral immune responseT cell immunityCellular immune responsesHumoral immune responsePrior vaccinationThird doseHumoral immunityImmune evasionOmicron variantInfectionInfection statusImmunityVaccinationNational studyResponseSARS-CoV-2 mRNA vaccines decouple anti-viral immunity from humoral autoimmunity
Jaycox J, Lucas C, Yildirim I, Dai Y, Wang E, Monteiro V, Lord S, Carlin J, Kita M, Buckner J, Ma S, Campbell M, Ko A, Omer S, Lucas C, Speake C, Iwasaki A, Ring A. SARS-CoV-2 mRNA vaccines decouple anti-viral immunity from humoral autoimmunity. Nature Communications 2023, 14: 1299. PMID: 36894554, PMCID: PMC9996559, DOI: 10.1038/s41467-023-36686-8.Peer-Reviewed Original ResearchConceptsVaccine-associated myocarditisAutoimmune patientsAutoantibody reactivitySARS-CoV-2 mRNA vaccinationVaccine-related adverse effectsSARS-CoV-2 immunitySARS-CoV-2 infectionAcute COVID-19Development of autoantibodiesCOVID-19 patientsAnti-viral immunityVirus-specific antibodiesCOVID-19 vaccineCOVID-19Humoral autoimmunityMRNA vaccinationAutoantibody responsePost vaccinationAutoantibody developmentAutoimmune diseasesHumoral responseHealthy individualsPatientsAntigen profilingAdverse effects
2022
Recognition and inhibition of SARS-CoV-2 by humoral innate immunity pattern recognition molecules
Stravalaci M, Pagani I, Paraboschi E, Pedotti M, Doni A, Scavello F, Mapelli S, Sironi M, Perucchini C, Varani L, Matkovic M, Cavalli A, Cesana D, Gallina P, Pedemonte N, Capurro V, Clementi N, Mancini N, Invernizzi P, Bayarri-Olmos R, Garred P, Rappuoli R, Duga S, Bottazzi B, Uguccioni M, Asselta R, Vicenzi E, Mantovani A, Garlanda C. Recognition and inhibition of SARS-CoV-2 by humoral innate immunity pattern recognition molecules. Nature Immunology 2022, 23: 275-286. PMID: 35102342, DOI: 10.1038/s41590-021-01114-w.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsC-Reactive ProteinCase-Control StudiesChlorocebus aethiopsComplement ActivationCoronavirus Nucleocapsid ProteinsCOVID-19FemaleGlycosylationHEK293 CellsHost-Pathogen InteractionsHumansImmunity, HumoralMaleMannose-Binding LectinPhosphoproteinsPolymorphism, GeneticProtein BindingReceptors, Pattern RecognitionSARS-CoV-2Serum Amyloid P-ComponentSignal TransductionSpike Glycoprotein, CoronavirusVero CellsConceptsFluid phase pattern recognition moleculesPattern recognition moleculesHumoral fluid phase pattern recognition moleculesMannose-binding lectinSARS-CoV-2Pentraxin 3Severe acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2Respiratory syndrome coronavirus 2Spike proteinDisease severity biomarkersSyndrome coronavirus 2Coronavirus disease 2019Long pentraxin 3Antibody-like functionsVariants of concernRecognition moleculesHumoral armSeverity biomarkersCoronavirus 2Disease 2019Innate immunityDisease severityComplement activationTranslational implications
2021
Impact of circulating SARS-CoV-2 variants on mRNA vaccine-induced immunity
Lucas C, Vogels CBF, Yildirim I, Rothman JE, Lu P, Monteiro V, Gehlhausen JR, Campbell M, Silva J, Tabachnikova A, Peña-Hernandez MA, Muenker MC, Breban MI, Fauver JR, Mohanty S, Huang J, Shaw A, Ko A, Omer S, Grubaugh N, Iwasaki A. Impact of circulating SARS-CoV-2 variants on mRNA vaccine-induced immunity. Nature 2021, 600: 523-529. PMID: 34634791, PMCID: PMC9348899, DOI: 10.1038/s41586-021-04085-y.Peer-Reviewed Original ResearchConceptsSARS-CoV-2 variantsMRNA vaccine-induced immunityT-cell activation markersSARS-CoV-2 antibodiesSecond vaccine doseVaccine-induced immunityCell activation markersT cell responsesHigh antibody titresSARS-CoV-2Vaccine boosterVaccine doseActivation markersVaccine dosesHumoral immunityAntibody titresMRNA vaccinesVitro stimulationNeutralization capacityNeutralization responseCell responsesE484KNucleocapsid peptideAntibody-binding sitesGreater reductionAdaptive immune determinants of viral clearance and protection in mouse models of SARS-CoV-2
Israelow B, Mao T, Klein J, Song E, Menasche B, Omer SB, Iwasaki A. Adaptive immune determinants of viral clearance and protection in mouse models of SARS-CoV-2. Science Immunology 2021, 6: eabl4509. PMID: 34623900, PMCID: PMC9047536, DOI: 10.1126/sciimmunol.abl4509.Peer-Reviewed Original ResearchConceptsSARS-CoV-2Viral clearanceImmune determinantsMouse modelSevere acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2Respiratory syndrome coronavirus 2Cellular adaptive immunitySyndrome coronavirus 2Vivo protective capacityVariants of concernMRNA vaccinationHomologous infectionCellular immunityConvalescent miceCoronavirus 2Antibody responsePrimary infectionEffective vaccineAdaptive immunityConfer protectionInfectionNatural infectionProtective capacityClearanceCD4+ 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 nomenclatureCytokinesImmunityAntibodiesDelayed production of neutralizing antibodies correlates with fatal COVID-19
Lucas C, Klein J, Sundaram ME, Liu F, Wong P, Silva J, Mao T, Oh JE, Mohanty S, Huang J, Tokuyama M, Lu P, Venkataraman A, Park A, Israelow B, Vogels CBF, Muenker MC, Chang CH, Casanovas-Massana A, Moore AJ, Zell J, Fournier JB, Wyllie A, Campbell M, Lee A, Chun H, Grubaugh N, Schulz W, Farhadian S, Dela Cruz C, Ring A, Shaw A, Wisnewski A, Yildirim I, Ko A, Omer S, Iwasaki A. Delayed production of neutralizing antibodies correlates with fatal COVID-19. Nature Medicine 2021, 27: 1178-1186. PMID: 33953384, PMCID: PMC8785364, DOI: 10.1038/s41591-021-01355-0.Peer-Reviewed Original ResearchConceptsDeceased patientsAntibody levelsAntibody responseDisease severityAnti-S IgG levelsCOVID-19 disease outcomesFatal COVID-19Impaired viral controlWorse clinical progressionWorse disease severitySevere COVID-19Length of hospitalizationImmunoglobulin G levelsHumoral immune responseCoronavirus disease 2019COVID-19 mortalityCOVID-19Domain (RBD) IgGSeroconversion kineticsDisease courseIgG levelsClinical parametersClinical progressionHumoral responseDisease onsetRoles of Bone Morphogenetic Protein Receptor 1A in Germinal Centers and Long-Lived Humoral Immunity
Tomayko MM, Karaaslan S, Lainez B, Conter LJ, Song E, Venkatesan S, Mishina Y, Shlomchik MJ. Roles of Bone Morphogenetic Protein Receptor 1A in Germinal Centers and Long-Lived Humoral Immunity. ImmunoHorizons 2021, 5: 284-297. PMID: 33975878, PMCID: PMC12221147, DOI: 10.4049/immunohorizons.2100019.Peer-Reviewed Original ResearchConceptsBone marrow-resident plasma cellsBone morphogenetic protein receptor 1AMemory B cellsMultiple stem cell populationsGene deletionStrong selective pressureGC B cellsStem cell populationGerminal centersB cellsReceptor 1aSelective pressureExpression studiesResultant establishmentNovel roleClass-switched memory B cellsEGFP reporter miceSex-Biased Aging Effects on Ig Somatic Hypermutation Targeting
Cui A, Chawla DG, Kleinstein SH. Sex-Biased Aging Effects on Ig Somatic Hypermutation Targeting. The Journal Of Immunology 2021, 206: 101-108. PMID: 33288546, PMCID: PMC8582005, DOI: 10.4049/jimmunol.2000576.Peer-Reviewed Original ResearchConceptsOlder individualsDNA mismatch repair genesSex groupsObserved clinical differencesMismatch repair genesB cell IgDecreased expression levelDNA repair activityImmunologic responseClinical differencesAb responsesFemale human subjectsOld maleAged individualsImpaired levelDifferent agesYounger counterpartsPhase ILargest fold changeYoung individualsError-prone DNA repair activityExpression levelsHuman subjectsMutation patternsRepair activity
2020
The kinetics of humoral response and its relationship with the disease severity in COVID-19
Ren L, Zhang L, Chang D, Wang J, Hu Y, Chen H, Guo L, Wu C, Wang C, Wang Y, Wang Y, Wang G, Yang S, Dela Cruz CS, Sharma L, Wang L, Zhang D, Wang J. The kinetics of humoral response and its relationship with the disease severity in COVID-19. Communications Biology 2020, 3: 780. PMID: 33311543, PMCID: PMC7733479, DOI: 10.1038/s42003-020-01526-8.Peer-Reviewed Original ResearchConceptsHumoral responseDisease severityReceptor-binding domainAntibody titersSpike proteinSevere acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2COVID-19Respiratory syndrome coronavirus 2Titers of NAbsGeometric mean titersCOVID-19 patientsSyndrome coronavirus 2Coronavirus disease 2019Disease courseMean titersCoronavirus 2Antibody responseIgG antibodiesRisk factorsIg levelsImmunoglobulin ADisease 2019Severe casesModerate infectionsAn Ixodes scapularis Protein Disulfide Isomerase Contributes to Borrelia burgdorferi Colonization of the Vector
Cao Y, Rosen C, Arora G, Gupta A, Booth CJ, Murfin KE, Cerny J, Lopez A, Chuang YM, Tang X, Pal U, Ring A, Narasimhan S, Fikrig E. An Ixodes scapularis Protein Disulfide Isomerase Contributes to Borrelia burgdorferi Colonization of the Vector. Infection And Immunity 2020, 88: 10.1128/iai.00426-20. PMID: 32928964, PMCID: PMC7671890, DOI: 10.1128/iai.00426-20.Peer-Reviewed Original ResearchConceptsTick gutTick bite siteVector-host interfaceAbility of spirochetesProtein disulfide isomerase A3Infected vertebrate hostsInflammatory responseBite siteLyme diseaseVertebrate hostsGutTick proteinsAdditional targetsMiceSpirochete life cycleSpirochete survivalArthropod vectorsSpirochetesRNA interferenceIllnessTicksDimethyl fumarate treatment shifts the immune environment toward an anti-inflammatory cell profile while maintaining protective humoral immunity
Longbrake EE, Mao-Draayer Y, Cascione M, Zielinski T, Bame E, Brassat D, Chen C, Kapadia S, Mendoza JP, Miller C, Parks B, Xing D, Robertson D. Dimethyl fumarate treatment shifts the immune environment toward an anti-inflammatory cell profile while maintaining protective humoral immunity. Multiple Sclerosis Journal 2020, 27: 883-894. PMID: 32716690, PMCID: PMC8023410, DOI: 10.1177/1352458520937282.Peer-Reviewed Original ResearchConceptsDelayed-release dimethyl fumarateAbsolute lymphocyte countT cellsMedian absolute lymphocyte countEffector memory T cellsDimethyl fumarate treatmentPhase 3b studyTotal T cellsAdverse event ratesMemory T cellsProtective humoral immunityForms of MSDMF BIDLymphocyte subsetsAdverse eventsLymphocyte countTotal IgAImmune environmentImmunoglobulin levelsNaive CD4Sustained efficacyHumoral immunityFumarate treatmentSubclass levelsCount changes
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