2020
Position-Dependent Differential Targeting of Somatic Hypermutation
Zhou JQ, Kleinstein SH. Position-Dependent Differential Targeting of Somatic Hypermutation. The Journal Of Immunology 2020, 205: 3468-3479. PMID: 33188076, PMCID: PMC7726104, DOI: 10.4049/jimmunol.2000496.Peer-Reviewed Original ResearchConceptsSomatic hypermutationSHM targetingIg sequencesSame DNA motifTranscription start siteAllele-specific effectsInfluence of selectionGene familyVariable gene familiesDNA motifsSequence neighborhoodError-prone repairStart siteAb diversityDNA lesionsDifferential targetingUnique motifMotifSequenceTargetingHypermutationEffective humoral immunityIntrinsic biasesAffinity maturationLarge collection
2016
A Model of Somatic Hypermutation Targeting in Mice Based on High-Throughput Ig Sequencing Data
Cui A, Di Niro R, Vander Heiden JA, Briggs AW, Adams K, Gilbert T, O'Connor KC, Vigneault F, Shlomchik MJ, Kleinstein SH. A Model of Somatic Hypermutation Targeting in Mice Based on High-Throughput Ig Sequencing Data. The Journal Of Immunology 2016, 197: 3566-3574. PMID: 27707999, PMCID: PMC5161250, DOI: 10.4049/jimmunol.1502263.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsB-LymphocytesCells, CulturedClonal Selection, Antigen-MediatedDNA RepairFemaleGerminal CenterHigh-Throughput Nucleotide SequencingHumansImmunoglobulin Heavy ChainsImmunoglobulin Variable RegionMiceMice, Inbred BALB CMice, TransgenicModels, GeneticMutationMutation RateSomatic Hypermutation, ImmunoglobulinConceptsSpecific DNA motifsSimilar biological processesObserved mutation patternDNA repair activityIg sequencesNonfunctional sequencesDNA motifsMutation patternsHigh mutation frequencySelection pressureUnselected mutationsSequencing dataBiological processesFunctional sequencesRepair activityTransition mutationsSomatic hypermutation patternsGerminal center B cellsSomatic hypermutationNext-generation methodsHypermutation patternsMutation frequencyMutationsSequenceMotif
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
2011
Somatic hypermutation targeting is influenced by location within the immunoglobulin V region
Cohen RM, Kleinstein SH, Louzoun Y. Somatic hypermutation targeting is influenced by location within the immunoglobulin V region. Molecular Immunology 2011, 48: 1477-1483. PMID: 21592579, PMCID: PMC3109224, DOI: 10.1016/j.molimm.2011.04.002.Peer-Reviewed Original ResearchConceptsObserved mutation patternSpecific DNA motifsBiased codon usageImmunoglobulin V genesMutation accumulationGene positionCodon usageMutation patternsDNA motifsPositive selectionPosition-specific effectsImmunoglobulin V regionsNegative selectionB cellsMutationsMutation frequencyV geneGenesPeripheral B cellsSubstitution typeV regionsTargetingSpecific targetingCellsSequence
2006
Mutation parameters from DNA sequence data using graph theoretic measures on lineage trees
Magori-Cohen R, Louzoun Y, Kleinstein SH. Mutation parameters from DNA sequence data using graph theoretic measures on lineage trees. Bioinformatics 2006, 22: e332-e340. PMID: 16873490, DOI: 10.1093/bioinformatics/btl239.Peer-Reviewed Original ResearchConceptsLineage treesDNA sequencesDNA sequence dataSomatic hypermutationMaximum likelihood analysisTree shapeBioinformatics methodsSequence dataLethal mutationsMutation rateNumber of generationsLikelihood analysisMutation parametersB cellsSynthetic treeClonal expansionTreesSequenceMutationsHypermutationAffinity maturationCellsImportant linkClonesUnexpected locations
2003
Why are there so few key mutant clones? The influence of stochastic selection and blocking on affinity maturation in the germinal center
Kleinstein SH, Singh JP. Why are there so few key mutant clones? The influence of stochastic selection and blocking on affinity maturation in the germinal center. International Immunology 2003, 15: 871-884. PMID: 12807826, DOI: 10.1093/intimm/dxg085.sgm.Peer-Reviewed Original Research