Featured Publications
The RAG1 N-terminal region regulates the efficiency and pathways of synapsis for V(D)J recombination
Beilinson HA, Glynn RA, Yadavalli AD, Xiao J, Corbett E, Saribasak H, Arya R, Miot C, Bhattacharyya A, Jones JM, Pongubala JMR, Bassing CH, Schatz DG. The RAG1 N-terminal region regulates the efficiency and pathways of synapsis for V(D)J recombination. Journal Of Experimental Medicine 2021, 218: e20210250. PMID: 34402853, PMCID: PMC8374863, DOI: 10.1084/jem.20210250.Peer-Reviewed Original Research
2020
Disease-associated CTNNBL1 mutation impairs somatic hypermutation by decreasing nuclear AID
Kuhny M, Forbes LR, Çakan E, Vega-Loza A, Kostiuk V, Dinesh RK, Glauzy S, Stray-Pedersen A, Pezzi AE, Hanson IC, Vargas-Hernandez A, Xu ML, Akdemir Z, Jhangiani SN, Muzny DM, Gibbs RA, Lupski JR, Chinn IK, Schatz DG, Orange JS, Meffre E. Disease-associated CTNNBL1 mutation impairs somatic hypermutation by decreasing nuclear AID. Journal Of Clinical Investigation 2020, 130: 4411-4422. PMID: 32484799, PMCID: PMC7410074, DOI: 10.1172/jci131297.Peer-Reviewed Original ResearchConceptsB cellsActivation-induced cytidine deaminaseHealthy donor counterpartsIsotype-switched B cellsCommon variable immunodeficiencyMemory B cellsSomatic hypermutationAutoimmune cytopeniasDecreased incidenceVariable immunodeficiencyB cell linesUnderlying molecular defectsNuclear AIDPatient's EBVRamos B cellsPatientsProtein 1Cell linesMolecular defectsCellsCytidine deaminaseMutations
2019
Intra-Vκ Cluster Recombination Shapes the Ig Kappa Locus Repertoire
Shinoda K, Maman Y, Canela A, Schatz DG, Livak F, Nussenzweig A. Intra-Vκ Cluster Recombination Shapes the Ig Kappa Locus Repertoire. Cell Reports 2019, 29: 4471-4481.e6. PMID: 31875554, PMCID: PMC8214342, DOI: 10.1016/j.celrep.2019.11.088.Peer-Reviewed Original ResearchConceptsDNA double-strand breaksRecombination signal sequencesVκ gene segmentsGene segmentsDouble-strand breaksVariable gene segmentsRAG proteinsSignal sequenceV-J rearrangementRecombination eventsSpacer regionVκ-JκRecombinationLevels of breakageComplete absenceProteinLarge fractionDeletionJκSequence
2015
Mechanisms of clonal evolution in childhood acute lymphoblastic leukemia
Swaminathan S, Klemm L, Park E, Papaemmanuil E, Ford A, Kweon SM, Trageser D, Hasselfeld B, Henke N, Mooster J, Geng H, Schwarz K, Kogan SC, Casellas R, Schatz DG, Lieber MR, Greaves MF, Müschen M. Mechanisms of clonal evolution in childhood acute lymphoblastic leukemia. Nature Immunology 2015, 16: 766-774. PMID: 25985233, PMCID: PMC4475638, DOI: 10.1038/ni.3160.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAnimalsAntibody DiversityB-LymphocytesChildChild, PreschoolClonal EvolutionCytidine DeaminaseDNA-Binding ProteinsFemaleFlow CytometryHomeodomain ProteinsHumansImmunoblottingInfantMaleMice, Inbred NODMice, KnockoutMice, SCIDMice, TransgenicMicroscopy, FluorescencePrecursor Cell Lymphoblastic Leukemia-LymphomaPrecursor Cells, B-LymphoidReverse Transcriptase Polymerase Chain ReactionTumor Cells, Cultured
2012
Clonal allelic predetermination of immunoglobulin-κ rearrangement
Farago M, Rosenbluh C, Tevlin M, Fraenkel S, Schlesinger S, Masika H, Gouzman M, Teng G, Schatz D, Rais Y, Hanna JH, Mildner A, Jung S, Mostoslavsky G, Cedar H, Bergman Y. Clonal allelic predetermination of immunoglobulin-κ rearrangement. Nature 2012, 490: 561-565. PMID: 23023124, DOI: 10.1038/nature11496.Peer-Reviewed Original ResearchDendritic cell–mediated activation-induced cytidine deaminase (AID)–dependent induction of genomic instability in human myeloma
Koduru S, Wong E, Strowig T, Sundaram R, Zhang L, Strout MP, Flavell RA, Schatz DG, Dhodapkar KM, Dhodapkar MV. Dendritic cell–mediated activation-induced cytidine deaminase (AID)–dependent induction of genomic instability in human myeloma. Blood 2012, 119: 2302-2309. PMID: 22234692, PMCID: PMC3311257, DOI: 10.1182/blood-2011-08-376236.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlotting, WesternCell Line, TumorCell SurvivalCells, CulturedCoculture TechniquesCytidine DeaminaseDendritic CellsDNA Breaks, Double-StrandedFemaleGene Expression Regulation, EnzymologicGene Expression Regulation, NeoplasticGenomic InstabilityHumansInterleukin Receptor Common gamma SubunitMiceMice, Inbred NODMice, KnockoutMice, SCIDMultiple MyelomaNF-kappa BRANK LigandReverse Transcriptase Polymerase Chain ReactionTransplantation, HeterologousTumor Cells, CulturedConceptsInduction of AIDMultiple myelomaTumor microenvironmentTumor cellsReceptor activatorActivation-induced cytidine deaminaseDendritic cell infiltrationCapacity of DCPrimary MM cellsNF-κB/receptor activatorGenetics of tumorsGrowth of tumorsGenomic damageMyeloma cell linesRANKL inhibitionPlasmacytoid DCsIndolent behaviorCell infiltrationMM cellsHuman myelomaCytidine deaminaseMyelomaDNA double-strand breaksGenomic instabilityCell lines
2010
Promoters, enhancers, and transcription target RAG1 binding during V(D)J recombination
Ji Y, Little AJ, Banerjee JK, Hao B, Oltz EM, Krangel MS, Schatz DG. Promoters, enhancers, and transcription target RAG1 binding during V(D)J recombination. Journal Of Experimental Medicine 2010, 207: 2809-2816. PMID: 21115692, PMCID: PMC3005232, DOI: 10.1084/jem.20101136.Peer-Reviewed Original ResearchMeSH KeywordsAcetylationAnimalsBinding, CompetitiveChromatin ImmunoprecipitationDNAEnhancer Elements, GeneticFemaleGene RearrangementGenes, ImmunoglobulinGenotypeHistonesHMGB1 ProteinHomeodomain ProteinsMaleMiceMice, Inbred C57BLMice, KnockoutPromoter Regions, GeneticProtein BindingReceptors, Antigen, T-Cell, alpha-betaRecombination, GeneticTranscription, GeneticVDJ Recombinases
1997
αβ Lineage‐committed thymocytes can be rescued by the γδ T cell receptor (TCR) in the absence of TCR β chain
Livák F, Wilson A, MacDonald H, Schatz D. αβ Lineage‐committed thymocytes can be rescued by the γδ T cell receptor (TCR) in the absence of TCR β chain. European Journal Of Immunology 1997, 27: 2948-2958. PMID: 9394823, DOI: 10.1002/eji.1830271130.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell DifferentiationFemaleGene Expression RegulationGene Rearrangement, alpha-Chain T-Cell Antigen ReceptorMiceMice, Inbred AKRMice, Inbred C57BLMice, KnockoutMice, TransgenicModels, ImmunologicalReceptors, Antigen, T-Cell, alpha-betaReceptors, Antigen, T-Cell, gamma-deltaThymus GlandT-Lymphocyte SubsetsTransgenesConceptsT cell receptorLineage commitmentT cell lineage commitmentCell lineage commitmentAlpha beta T cell developmentTCR beta proteinGamma delta T cell lineagesAlpha beta lineageT cell developmentCell receptorTCR-mediated selectionGene rearrangementsCell lineagesT cellsΑβ lineageCell developmentTCR gammaAlpha betaT-cell lineageBeta lineageLineagesGamma delta T-cell receptorTCR β chainGamma delta T cellsDelta T-cell receptor
1996
Neoteny in Lymphocytes: Rag1 and Rag2 Expression in Germinal Center B Cells
Han S, Zheng B, Schatz D, Spanopoulou E, Kelsoe G. Neoteny in Lymphocytes: Rag1 and Rag2 Expression in Germinal Center B Cells. Science 1996, 274: 2094-2097. PMID: 8953043, DOI: 10.1126/science.274.5295.2094.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsB-LymphocytesDNA NucleotidyltransferasesDNA-Binding ProteinsFemaleGene ExpressionGene RearrangementGenes, ImmunoglobulinGenes, RAG-1Germinal CenterHomeodomain ProteinsImmunizationImmunoglobulin Class SwitchingLymphocyte ActivationMiceMice, Inbred C57BLPolymerase Chain ReactionProtein BiosynthesisProteinsVDJ RecombinasesConceptsGerminal center B cellsAntigen receptor genesT cell antigen receptor genesRAG2 proteinsB cellsRAG2 geneRAG genesRAG2 expressionFunctional immunoglobulinPeyer's patch germinal centersMessenger RNAGenesRAG1Receptor geneActivated B cellsNormal adult animalsLymphocyte populationsImmature lymphocytesGerminal centersBone marrowMurine splenicAntibody repertoireCellsAdult animalsExpressionTransient restoration of gene rearrangement at multiple T cell receptor loci in gamma-irradiated scid mice.
Livák F, Welsh SC, Guidos CJ, Crispe IN, Danska JS, Schatz DG. Transient restoration of gene rearrangement at multiple T cell receptor loci in gamma-irradiated scid mice. Journal Of Experimental Medicine 1996, 184: 419-428. PMID: 8760795, PMCID: PMC2192694, DOI: 10.1084/jem.184.2.419.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnimals, NewbornBase SequenceFemaleGamma RaysGene Rearrangement, alpha-Chain T-Cell Antigen ReceptorGene Rearrangement, delta-Chain T-Cell Antigen ReceptorMaleMiceMice, Inbred AKRMice, Inbred BALB CMice, Inbred C57BLMice, SCIDMolecular Sequence DataReceptors, Antigen, T-CellRecombination, GeneticRestriction MappingThymus GlandProductive T-cell receptor beta-chain gene rearrangement: coincident regulation of cell cycle and clonality during development in vivo.
Hoffman ES, Passoni L, Crompton T, Leu TM, Schatz DG, Koff A, Owen MJ, Hayday AC. Productive T-cell receptor beta-chain gene rearrangement: coincident regulation of cell cycle and clonality during development in vivo. Genes & Development 1996, 10: 948-962. PMID: 8608942, DOI: 10.1101/gad.10.8.948.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, Differentiation, T-LymphocyteCell CycleCell SeparationClone CellsCyclinsDNA-Binding ProteinsFemaleFlow CytometryFluorescent Antibody Technique, IndirectGene Expression Regulation, DevelopmentalGene Rearrangement, beta-Chain T-Cell Antigen ReceptorHomeodomain ProteinsHyaluronan ReceptorsMiceMice, Inbred C57BLProteinsReceptors, Antigen, T-Cell, alpha-betaReceptors, Interleukin-2Retinoblastoma ProteinRNA, MessengerThymus GlandT-LymphocytesConceptsTCRbeta chain genesBeta selectionT-cell receptor beta-chain locusChain geneTCRbeta chain gene rearrangementAlpha beta T cell developmentProductive gene rearrangementHyperphosphorylation of RbGene rearrangementsTCR gene rearrangementsTransition of thymocytesTCRbeta gene rearrangementT cell developmentRegulation of p27Coincident regulationBeta-chain locusPopulation of cellsTCR lociCell cycleCdc2 activityCDK2 activityTCRbeta selectionCyclin AThymocyte expansionCell phenotypeThe half-life of RAG-1 protein in precursor B cells is increased in the absence of RAG-2 expression.
Grawunder U, Schatz DG, Leu TM, Rolink A, Melchers F. The half-life of RAG-1 protein in precursor B cells is increased in the absence of RAG-2 expression. Journal Of Experimental Medicine 1996, 183: 1731-1737. PMID: 8666930, PMCID: PMC2192496, DOI: 10.1084/jem.183.4.1731.Peer-Reviewed Original Research
1995
Down-regulation of RAG1 and RAG2 gene expression in PreB cells after functional immunoglobulin heavy chain rearrangement
Grawunder U, Leu T, Schatz D, Werner A, Rolink A, Melchers F, Winkler T. Down-regulation of RAG1 and RAG2 gene expression in PreB cells after functional immunoglobulin heavy chain rearrangement. Immunity 1995, 3: 601-608. PMID: 7584150, DOI: 10.1016/1074-7613(95)90131-0.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBase SequenceB-LymphocytesCell DifferentiationCell LineDNA-Binding ProteinsDown-RegulationFemaleFlow CytometryGene Rearrangement, B-LymphocyteHomeodomain ProteinsImmunoglobulin Heavy ChainsMiceMice, Inbred C57BLMice, Inbred DBAMice, Inbred StrainsMolecular Sequence DataPolymerase Chain ReactionProtein BiosynthesisProteinsProto-Oncogene Proteins c-kitReceptors, Antigen, B-CellRNA, MessengerConceptsRAG2 gene expressionPreB cellsGene expressionFunctional immunoglobulin genesPreB-II cellsPreB cell receptorB cell developmentCell cycle statusHeavy chain allelesRAG2 proteinsPostranscriptional levelImmature B cellsRAG genesGene productsTranscriptional levelProductive rearrangementsMouse bone marrowCell developmentDifferential surface expressionImmunoglobulin genesRAG1Cell surfaceRAG2 mRNAGenesCycle statusIn-frame TCR δ gene rearrangements play a critical role in the αβ/γδ T cell lineage decision
Livak F, Petrie H, Crisps I, Schatz D. In-frame TCR δ gene rearrangements play a critical role in the αβ/γδ T cell lineage decision. Immunity 1995, 2: 617-627. PMID: 7796295, DOI: 10.1016/1074-7613(95)90006-3.Peer-Reviewed Original ResearchConceptsT cell lineage decisionsCell lineage decisionsLineage decisionsRandom gene rearrangementsSouthern blot analysisT cell receptor complexCell receptor complexGene rearrangementsDelta locusLocus sequenceGamma delta lineageReceptor complexT cell receptorBlot analysisDistinct precursorsCommon precursorCell receptorCritical roleDelta rearrangementsDelta lineageRearrangementΔ gene rearrangementAlpha betaT cellsGamma delta T-cell receptor
1990
RAG-1 and RAG-2, Adjacent Genes That Synergistically Activate V(D)J Recombination
Oettinger M, Schatz D, Gorka C, Baltimore D. RAG-1 and RAG-2, Adjacent Genes That Synergistically Activate V(D)J Recombination. Science 1990, 248: 1517-1523. PMID: 2360047, DOI: 10.1126/science.2360047.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsBase SequenceBiological EvolutionCattleCell LineChickensCricetinaeDNADNA NucleotidyltransferasesDNA-Binding ProteinsDogsFemaleGene Rearrangement, B-LymphocyteGene Rearrangement, T-LymphocyteHomeodomain ProteinsHumansMaleMiceMolecular Sequence DataMultigene FamilyNuclear ProteinsNucleic Acid HybridizationOpossumsProteinsRabbitsRecombination, GeneticRestriction MappingTransfectionTurtlesVDJ RecombinasesConceptsRAG-2RAG-1Adjacent genesRecombinase activityFrequency of recombinationPutative proteinUntranslated sequenceSingle exonGenomic rearrangementsExpression patternsVast repertoireGenesComplementary DNAAmino acidsT cell receptorCell receptorRecombinationSequenceKilobasesExonsCotransfectionRecombinaseSpeciesProteinDNA