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
Long-lived antigen-induced IgM plasma cells demonstrate somatic mutations and contribute to long-term protection
Bohannon C, Powers R, Satyabhama L, Cui A, Tipton C, Michaeli M, Skountzou I, Mittler RS, Kleinstein SH, Mehr R, Lee FE, Sanz I, Jacob J. Long-lived antigen-induced IgM plasma cells demonstrate somatic mutations and contribute to long-term protection. Nature Communications 2016, 7: 11826. PMID: 27270306, PMCID: PMC4899631, DOI: 10.1038/ncomms11826.Peer-Reviewed Original ResearchMeSH KeywordsAdoptive TransferAmino Acid MotifsAnimalsAntigensComplementarity Determining RegionsCytidine DeaminaseGerminal CenterImmunityImmunoglobulin Heavy ChainsImmunoglobulin MMice, Inbred C57BLMutationNeutralization TestsOrthomyxoviridaeOrthomyxoviridae InfectionsPlasma CellsSomatic Hypermutation, ImmunoglobulinSpleenConceptsIgM plasma cellsIgG plasma cellsPlasma cellsGerminal centersBone marrowLethal virus challengeProtective host immunitySomatic mutationsActivation-induced cytidine deaminaseHumoral immunityProtective antibodiesVirus challengeLong-term protectionHost immunityB cellsAffinity maturationMarrowLifelong sourceImmunityAntibodiesCellsCytidine deaminaseMutationsReplacement mutationsSpleen
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 roundsSalmonella Infection Drives Promiscuous B Cell Activation Followed by Extrafollicular Affinity Maturation
Di Niro R, Lee SJ, Vander Heiden J, Elsner RA, Trivedi N, Bannock JM, Gupta NT, Kleinstein SH, Vigneault F, Gilbert TJ, Meffre E, McSorley SJ, Shlomchik MJ. Salmonella Infection Drives Promiscuous B Cell Activation Followed by Extrafollicular Affinity Maturation. Immunity 2015, 43: 120-131. PMID: 26187411, PMCID: PMC4523395, DOI: 10.1016/j.immuni.2015.06.013.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, MonoclonalB-LymphocytesClonal Selection, Antigen-MediatedGerminal CenterImmunoglobulin GLymphocyte ActivationMiceMice, Inbred BALB CMice, Inbred C57BLMice, KnockoutReceptors, Antigen, B-CellSalmonella InfectionsSalmonella typhimuriumSomatic Hypermutation, ImmunoglobulinSpleenConceptsB cell receptorExtrafollicular sitesGerminal centersAffinity maturationInfection of miceB cell responsesB cell activationDetectable antibodiesSomatic hypermutationExtrafollicular responseAntigen microarraysSalmonella infectionAntigen targetsCell activationSalmonella typhimuriumCell responsesBCR specificityFlow cytometryCell receptorMonoclonal antibodiesUndetectable affinityClonal selectionInfectionAntibodiesLaser microdissectionLong-lived IgM plasma cells confer host protection against viral challenge (LYM6P.717)
Bohannon C, Powers R, Satyabhama L, Cui A, Tipton C, Michaeli M, Mehr R, Mittler R, Kleinstein S, Sanz I, Jacob J. Long-lived IgM plasma cells confer host protection against viral challenge (LYM6P.717). The Journal Of Immunology 2015, 194: 135.5-135.5. DOI: 10.4049/jimmunol.194.supp.135.5.Peer-Reviewed Original Research
2011
Activated germinal centre B cells undergo directed migration.
O'Connor MJ, Hauser AE, Haberman AM, Kleinstein SH. Activated germinal centre B cells undergo directed migration. International Journal Of Data Mining And Bioinformatics 2011, 5: 321-31. PMID: 21805826, PMCID: PMC4343311, DOI: 10.1504/ijdmb.2011.040387.Peer-Reviewed Original Research
2009
Activated Germinal-Center B Cells Undergo Directed Migration
O'Connor M, Hauser A, Haberman A, Kleinstein S. Activated Germinal-Center B Cells Undergo Directed Migration. 2009, 327-331. DOI: 10.1109/bibm.2009.61.Peer-Reviewed Original Research
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