2020
Thymus-derived B cell clones persist in the circulation after thymectomy in myasthenia gravis
Jiang R, Hoehn KB, Lee CS, Pham MC, Homer RJ, Detterbeck FC, Aban I, Jacobson L, Vincent A, Nowak RJ, Kaminski HJ, Kleinstein SH, O'Connor KC. Thymus-derived B cell clones persist in the circulation after thymectomy in myasthenia gravis. Proceedings Of The National Academy Of Sciences Of The United States Of America 2020, 117: 30649-30660. PMID: 33199596, PMCID: PMC7720237, DOI: 10.1073/pnas.2007206117.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAutoantibodiesBiomarkersB-LymphocytesClonal EvolutionClonal Selection, Antigen-MediatedDisease SusceptibilityFemaleHumansLymphocyte CountMaleMiddle AgedModels, BiologicalMyasthenia GravisRadioimmunoassayReceptors, CholinergicThymectomyThymus GlandV(D)J RecombinationYoung AdultConceptsB cell clonesMyasthenia gravisB cell repertoireB cellsCell clonesPlasma cellsCell repertoireAdditional immunosuppressive treatmentDiminished clinical responseThymic lymphofollicular hyperplasiaComplete stable remissionMajority of patientsAntigen-experienced B cellsRandomized clinical trialsClinical symptom measuresAChR autoantibodiesImmunosuppressive treatmentSteroid doseAutoantibody titersMG thymusClinical responseStable remissionClinical scoresAutoimmune diseasesClinical trials
2019
Inferred Allelic Variants of Immunoglobulin Receptor Genes: A System for Their Evaluation, Documentation, and Naming
Ohlin M, Scheepers C, Corcoran M, Lees WD, Busse CE, Bagnara D, Thörnqvist L, Bürckert JP, Jackson KJL, Ralph D, Schramm CA, Marthandan N, Breden F, Scott J, Matsen F, Greiff V, Yaari G, Kleinstein SH, Christley S, Sherkow JS, Kossida S, Lefranc MP, van Zelm MC, Watson CT, Collins AM. Inferred Allelic Variants of Immunoglobulin Receptor Genes: A System for Their Evaluation, Documentation, and Naming. Frontiers In Immunology 2019, 10: 435. PMID: 30936866, PMCID: PMC6431624, DOI: 10.3389/fimmu.2019.00435.Peer-Reviewed Original ResearchMeSH KeywordsAllelesBase SequenceDatabases, GeneticDatasets as TopicGene LibraryGenes, ImmunoglobulinGenetic VariationGerm-Line MutationHigh-Throughput Nucleotide SequencingHumansImmunoglobulin Heavy ChainsImmunoglobulin Variable RegionPolymerase Chain ReactionSequence AlignmentSequence Homology, Nucleic AcidTerminology as TopicV(D)J RecombinationVDJ ExonsConceptsGene databaseInternational ImMunoGeneTics information systemAdaptive immune receptor repertoire sequencingLymphocyte receptor genesAllelic variantsGermline genesReceptor geneAIRR CommunityVertebrate speciesGenetic variationIg diversityAIRR-seq dataJ genesIg genesAllelic sequencesGenesIGHV genesEffector moleculesUnprecedented insightsB-cell lineageBiological interpretationT cell receptorReference databaseGene variationRepertoire studies
2016
VDJML: a file format with tools for capturing the results of inferring immune receptor rearrangements
Toby IT, Levin MK, Salinas EA, Christley S, Bhattacharya S, Breden F, Buntzman A, Corrie B, Fonner J, Gupta NT, Hershberg U, Marthandan N, Rosenfeld A, Rounds W, Rubelt F, Scarborough W, Scott JK, Uduman M, Vander Heiden JA, Scheuermann RH, Monson N, Kleinstein SH, Cowell LG. VDJML: a file format with tools for capturing the results of inferring immune receptor rearrangements. BMC Bioinformatics 2016, 17: 333. PMID: 27766961, PMCID: PMC5073965, DOI: 10.1186/s12859-016-1214-3.Peer-Reviewed Original ResearchRAG1 targeting in the genome is dominated by chromatin interactions mediated by the non-core regions of RAG1 and RAG2
Maman Y, Teng G, Seth R, Kleinstein SH, Schatz DG. RAG1 targeting in the genome is dominated by chromatin interactions mediated by the non-core regions of RAG1 and RAG2. Nucleic Acids Research 2016, 44: 9624-9637. PMID: 27436288, PMCID: PMC5175335, DOI: 10.1093/nar/gkw633.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBinding SitesChromatinChromatin ImmunoprecipitationGenomeGenomic InstabilityHigh-Throughput Nucleotide SequencingHistonesHomeodomain ProteinsHumansMiceNucleotide MotifsPromoter Regions, GeneticProtein BindingProtein Interaction Domains and MotifsRecombination, GeneticV(D)J RecombinationConceptsAntigen receptor lociNon-core regionsReceptor locusPlant homeodomain (PHD) fingerChIP-seq dataWide bindingChromatin interactionsAdditional chromatinLysine 4Off-target activityGenomic featuresHistone 3Novel roleRAG1LociChromatinGenomeRAG2Observed patternsDistinct modesBindingH3K4me3H3K27acEndonucleaseRelative contributionIndividual heritable differences result in unique cell lymphocyte receptor repertoires of naïve and antigen-experienced cells
Rubelt F, Bolen CR, McGuire HM, Heiden J, Gadala-Maria D, Levin M, M. Euskirchen G, Mamedov MR, Swan GE, Dekker CL, Cowell LG, Kleinstein SH, Davis MM. Individual heritable differences result in unique cell lymphocyte receptor repertoires of naïve and antigen-experienced cells. Nature Communications 2016, 7: 11112. PMID: 27005435, PMCID: PMC5191574, DOI: 10.1038/ncomms11112.Peer-Reviewed Original ResearchConceptsChromosome-wide levelJ gene segmentsAntigen receptor repertoireHeritable mechanismsSingle chromosomeEpigenetic differencesHeritable differencesReceptor repertoireLymphocyte receptor repertoireGene segmentsAdaptive immune systemHeritable factorsRepertoireRelative usageAntigen-experienced cellsThymic selectionCellsImmune systemChromosomesSignificant variationCDR3 regionMonozygotic twinsRearrangementT lymphocyte subsets
2015
Automated analysis of high-throughput B-cell sequencing data reveals a high frequency of novel immunoglobulin V gene segment alleles
Gadala-Maria D, Yaari G, Uduman M, Kleinstein SH. Automated analysis of high-throughput B-cell sequencing data reveals a high frequency of novel immunoglobulin V gene segment alleles. Proceedings Of The National Academy Of Sciences Of The United States Of America 2015, 112: e862-e870. PMID: 25675496, PMCID: PMC4345584, DOI: 10.1073/pnas.1417683112.Peer-Reviewed Original Research
2014
High-resolution antibody dynamics of vaccine-induced immune responses
Laserson U, Vigneault F, Gadala-Maria D, Yaari G, Uduman M, Vander Heiden J, Kelton W, Jung S, Liu Y, Laserson J, Chari R, Lee JH, Bachelet I, Hickey B, Lieberman-Aiden E, Hanczaruk B, Simen BB, Egholm M, Koller D, Georgiou G, Kleinstein SH, Church GM. High-resolution antibody dynamics of vaccine-induced immune responses. Proceedings Of The National Academy Of Sciences Of The United States Of America 2014, 111: 4928-4933. PMID: 24639495, PMCID: PMC3977259, DOI: 10.1073/pnas.1323862111.Peer-Reviewed Original Research