2017
Hierarchical Clustering Can Identify B Cell Clones with High Confidence in Ig Repertoire Sequencing Data
Gupta NT, Adams KD, Briggs AW, Timberlake SC, Vigneault F, Kleinstein SH. Hierarchical Clustering Can Identify B Cell Clones with High Confidence in Ig Repertoire Sequencing Data. The Journal Of Immunology 2017, 198: 2489-2499. PMID: 28179494, PMCID: PMC5340603, DOI: 10.4049/jimmunol.1601850.Peer-Reviewed Original Research
2015
The mutation patterns in B-cell immunoglobulin receptors reflect the influence of selection acting at multiple time-scales
Yaari G, Benichou JI, Vander Heiden J, Kleinstein SH, Louzoun Y. The mutation patterns in B-cell immunoglobulin receptors reflect the influence of selection acting at multiple time-scales. Philosophical Transactions Of The Royal Society B Biological Sciences 2015, 370: 20140242. PMID: 26194756, PMCID: PMC4528419, DOI: 10.1098/rstb.2014.0242.Peer-Reviewed Original ResearchMeSH KeywordsAntibody AffinityAntibody DiversityB-LymphocytesCell LineageClonal Selection, Antigen-MediatedComplementarity Determining RegionsGenes, ImmunoglobulinHumansImmunoglobulin Heavy ChainsImmunoglobulin Variable RegionModels, GeneticModels, ImmunologicalMutationReceptors, Antigen, B-CellSomatic Hypermutation, ImmunoglobulinTime FactorsConceptsLineage treesPositive selectionStrong selection pressureLong-term selectionInfluence of selectionGene familyVariable gene familiesComplementarity determining regionsClone membersMutation patternsSelection pressureB cell populationsImmunoglobulin genesB cellsFramework regionsSomatic hypermutationSomatic mutationsAffinity maturationMutationsClone sizeMaturation processLong trunkAffinity maturation processSignificant diversityMultiple rounds
2014
Influence of seasonal exposure to grass pollen on local and peripheral blood IgE repertoires in patients with allergic rhinitis
Wu YC, James LK, Vander Heiden J, Uduman M, Durham SR, Kleinstein SH, Kipling D, Gould HJ. Influence of seasonal exposure to grass pollen on local and peripheral blood IgE repertoires in patients with allergic rhinitis. Journal Of Allergy And Clinical Immunology 2014, 134: 604-612. PMID: 25171866, PMCID: PMC4151999, DOI: 10.1016/j.jaci.2014.07.010.Peer-Reviewed Original ResearchConceptsHealthy control subjectsNasal biopsy specimensAllergic rhinitisControl subjectsImmunoglobulin heavy chain geneBiopsy specimensIgE repertoireAllergic diseasesPeripheral bloodOngoing germinal center reactionsClonal relatednessNatural pollen exposureSeasonal allergic rhinitisPollen seasonRespiratory allergic diseasesIgH sequencesAntigen-driven selectionGerminal center reactionGrass pollen seasonBlood IgEAtopic statusIgG classAntibody classPatientsPollen exposureIntegrating B Cell Lineage Information into Statistical Tests for Detecting Selection in Ig Sequences
Uduman M, Shlomchik MJ, Vigneault F, Church GM, Kleinstein SH. Integrating B Cell Lineage Information into Statistical Tests for Detecting Selection in Ig Sequences. The Journal Of Immunology 2014, 192: 867-874. PMID: 24376267, PMCID: PMC4363135, DOI: 10.4049/jimmunol.1301551.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibody AffinityAntibody DiversityB-Lymphocyte SubsetsCell LineageClonal Selection, Antigen-MediatedComputer SimulationConfounding Factors, EpidemiologicGene Rearrangement, B-LymphocyteGenes, ImmunoglobulinHumansMiceModels, ImmunologicalModels, StatisticalROC CurveSequence Analysis, DNASomatic Hypermutation, ImmunoglobulinVDJ ExonsConceptsLineage treesHigh-throughput sequencing technologyLineage tree shapesCell lineage informationIg sequencesRatio of replacementTree-shape analysisStatistical frameworkSequence-based methodsBinomial statistical analysisExperimental data setsIndicators of selectionSequencing technologiesLineage informationSequencing depthNumber of generationsData setsHybrid methodVivo selectionSilent mutationsTree shapeStatistical testsSequenceShape analysisMutations
2008
Two levels of protection for the B cell genome during somatic hypermutation
Liu M, Duke JL, Richter DJ, Vinuesa CG, Goodnow CC, Kleinstein SH, Schatz DG. Two levels of protection for the B cell genome during somatic hypermutation. Nature 2008, 451: 841-845. PMID: 18273020, DOI: 10.1038/nature06547.Peer-Reviewed Original ResearchConceptsError-free DNA repairB cell genomeGenomic stabilityNumerous oncogenesDNA repairCell genomeBase excisionGenomeMismatch repairImmunoglobulin genesSomatic hypermutationWidespread mutationsHypermutationB-cell tumorsB-cell malignanciesHigh-affinity antibodiesB cellsGenesOncogeneLarge fractionDiversityVital roleMutationsEnzymeRepair