2024
Stochastic modeling of a gene regulatory network driving B cell development in germinal centers
Koshkin A, Herbach U, Martínez M, Gandrillon O, Crauste F. Stochastic modeling of a gene regulatory network driving B cell development in germinal centers. PLOS ONE 2024, 19: e0301022. PMID: 38547073, PMCID: PMC10977792, DOI: 10.1371/journal.pone.0301022.Peer-Reviewed Original ResearchMeSH KeywordsB-LymphocytesGene Expression ProfilingGene Regulatory NetworksGerminal CenterHumansSystems BiologyConceptsGene regulatory network structureGene regulatory networksGene expression dataExpression dataB cell differentiationSingle-cellAssociated with cell developmentGC B cell differentiationStages of B-cell differentiationB cell developmentSelection of B cellsGene regulationRegulatory networksTranscriptome dataSystems biologyHigh-affinity antibodiesRegulatory mechanismsCell developmentGenesAdaptive immune systemMRNA distributionPlasmablast stageGerminal centersDifferentiationImmune system
2023
Convergent evolution and B-cell recirculation in germinal centers in a human lymph node
Pelissier A, Stratigopoulou M, Donner N, Dimitriadis E, Bende R, Guikema J, Martinez M, van Noesel C. Convergent evolution and B-cell recirculation in germinal centers in a human lymph node. Life Science Alliance 2023, 6: e202301959. PMID: 37640448, PMCID: PMC10462906, DOI: 10.26508/lsa.202301959.Peer-Reviewed Original ResearchConceptsGerminal centersLymph nodesHuman lymph nodesGC responseHuman LNImmune responseDevelopment of autoimmune diseasesConvergent evolutionB cell clonesB cell recirculationEffective immune responseExpanded clonesLaser capture microdissectionPhylogenetic tree analysisIndividual germinal centersB cellsAutoimmune diseasesAntigen responseMouse modelModel antigenAntigenClonal diversityExploring the impact of clonal definition on B-cell diversity: implications for the analysis of immune repertoires
Pelissier A, Luo S, Stratigopoulou M, Guikema J, Martínez M. Exploring the impact of clonal definition on B-cell diversity: implications for the analysis of immune repertoires. Frontiers In Immunology 2023, 14: 1123968. PMID: 37138881, PMCID: PMC10150052, DOI: 10.3389/fimmu.2023.1123968.Peer-Reviewed Original ResearchConceptsClonal diversityB cell receptorB cellsB cell diversityHigh-throughput sequencing technologyAlignment-free methodsAnalysis of immune repertoiresAlignment-based methodsPatterns of variationB cell receptor sequencesSequencing technologiesClonal clustersClonal identificationB cell repertoireActivated B cellsAdaptive immune responsesDiversity indexHigh-throughput characterizationAdaptive immune systemShort sequencesClonal characterizationClonal familiesClonesRepertoire dataSomatic hypermutation
2021
Multiscale Modeling of Germinal Center Recapitulates the Temporal Transition From Memory B Cells to Plasma Cells Differentiation as Regulated by Antigen Affinity-Based Tfh Cell Help
Tejero E, Lashgari D, García-Valiente R, Gao X, Crauste F, Robert P, Meyer-Hermann M, Martínez M, van Ham S, Guikema J, Hoefsloot H, van Kampen A. Multiscale Modeling of Germinal Center Recapitulates the Temporal Transition From Memory B Cells to Plasma Cells Differentiation as Regulated by Antigen Affinity-Based Tfh Cell Help. Frontiers In Immunology 2021, 11: 620716. PMID: 33613551, PMCID: PMC7892951, DOI: 10.3389/fimmu.2020.620716.Peer-Reviewed Original ResearchMeSH KeywordsAsymmetric Cell DivisionB-LymphocytesCD40 AntigensCell LineageComputer SimulationGene Regulatory NetworksGerminal CenterHumansImmunologic MemoryInterferon Regulatory FactorsLymphopoiesisModels, ImmunologicalPlasma CellsPositive Regulatory Domain I-Binding Factor 1Proto-Oncogene Proteins c-bcl-6Signal TransductionT Follicular Helper CellsTime FactorsConceptsB cell to plasma cell differentiationAsymmetric divisionRegulatory interactions of transcription factorsPlasma cell differentiationInteraction of transcription factorsCore gene regulatory networkGene regulatory networksCell differentiationCell-fate decisionsTemporal switchB cell receptor affinityGerminal center reactionB cellsCD40 signaling pathwayRegulatory networksRegulatory interactionsTranscription factorsEffective immune protectionCenter reactionSignaling pathwayAdaptive immune systemT follicular helper cellsPlasma cell generationMemory B cellsMolecular modules
2019
A Probabilistic Model of the Germinal Center Reaction
Thomas M, Klein U, Lygeros J, Martínez M. A Probabilistic Model of the Germinal Center Reaction. Frontiers In Immunology 2019, 10: 689. PMID: 31001283, PMCID: PMC6456718, DOI: 10.3389/fimmu.2019.00689.Peer-Reviewed Original ResearchConceptsB cell differentiationMemory B cell differentiationSpecialized compartmentsAntibody genesPlasma cell differentiationFate selectionB cellsIndividual cell propertiesCell differentiationB cell maturationMolecular eventsEfficient stochastic simulationExtracellular dynamicsQuantitative stochastic modelMemory B cell formationAntigen affinityB cell formationGillespie algorithmDifferentiationCell propertiesCell productionMemory B cells
2012
Quantitative modeling of the terminal differentiation of B cells and mechanisms of lymphomagenesis
Martínez M, Corradin A, Klein U, Álvarez M, Toffolo G, di Camillo B, Califano A, Stolovitzky G. Quantitative modeling of the terminal differentiation of B cells and mechanisms of lymphomagenesis. Proceedings Of The National Academy Of Sciences Of The United States Of America 2012, 109: 2672-2677. PMID: 22308355, PMCID: PMC3289327, DOI: 10.1073/pnas.1113019109.Peer-Reviewed Original ResearchMeSH KeywordsB-LymphocytesCell DifferentiationGene Expression ProfilingHumansImmunologic MemoryLymphomaConceptsB-cell exitTranscriptional regulatory modulesTerminal differentiationTerminal differentiation of B cellsSelf-regulatory interactionsGene expression profiling dataMechanisms of lymphomagenesisExpression profiling dataMature human B cellsRegulatory modulesGene regulationT cell signalingB cellsCellular statesDifferentiation of B cellsHuman B cellsGerminal centersTumorigenic alterationsGenesQuantitative kinetic modelMemory B cellsAssociated with lymphomagenesisFeedback loopLymphomagenesisT cells