2018
Spatiotemporal segregation of human marginal zone and memory B cell populations in lymphoid tissue
Zhao Y, Uduman M, Siu JHY, Tull TJ, Sanderson JD, Wu YB, Zhou JQ, Petrov N, Ellis R, Todd K, Chavele KM, Guesdon W, Vossenkamper A, Jassem W, D’Cruz D, Fear DJ, John S, Scheel-Toellner D, Hopkins C, Moreno E, Woodman NL, Ciccarelli F, Heck S, Kleinstein SH, Bemark M, Spencer J. Spatiotemporal segregation of human marginal zone and memory B cell populations in lymphoid tissue. Nature Communications 2018, 9: 3857. PMID: 30242242, PMCID: PMC6155012, DOI: 10.1038/s41467-018-06089-1.Peer-Reviewed Original ResearchConceptsMemory B cellsMZ B cellsLymphoid tissueB cellsClassical memory B cellsMemory B cell populationsDistant lymphoid tissuesGut lymphoid tissueExpression of CD27Marginal zone B cellsB cell poolHuman memory B cellsB cell populationsSomatic mutationsMicroanatomical nichesGerminal centersPhenotypic progressionCell poolMass cytometryCell populationsIGHV repertoireTissueMarginal zoneCellsPopulation
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 roundsLong-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
2014
Shared VH1-46 gene usage by pemphigus vulgaris autoantibodies indicates common humoral immune responses among patients
Cho MJ, Lo AS, Mao X, Nagler AR, Ellebrecht CT, Mukherjee EM, Hammers CM, Choi EJ, Sharma PM, Uduman M, Li H, Rux AH, Farber SA, Rubin CB, Kleinstein SH, Sachais BS, Posner MR, Cavacini LA, Payne AS. Shared VH1-46 gene usage by pemphigus vulgaris autoantibodies indicates common humoral immune responses among patients. Nature Communications 2014, 5: 4167. PMID: 24942562, PMCID: PMC4120239, DOI: 10.1038/ncomms5167.Peer-Reviewed Original ResearchConceptsHumoral immune responsePemphigus vulgarisGene usageImmune responseAnti-Dsg3 antibodiesSomatic mutationsRequirement of mutationsPemphigus vulgaris autoantibodiesBlistering diseasePV patientsVH gene usagePatientsDesmoglein 3Unrelated patientsAutoAbsAutoantibodiesAutoreactivityDsg3MutationsGermline sequencesAbReplacement mutationsVDJ recombinationDiseaseAntibodies
2013
Multiple Transcription Factor Binding Sites Predict AID Targeting in Non-Ig Genes
Duke JL, Liu M, Yaari G, Khalil AM, Tomayko MM, Shlomchik MJ, Schatz DG, Kleinstein SH. Multiple Transcription Factor Binding Sites Predict AID Targeting in Non-Ig Genes. The Journal Of Immunology 2013, 190: 3878-3888. PMID: 23514741, PMCID: PMC3689293, DOI: 10.4049/jimmunol.1202547.Peer-Reviewed Original ResearchConceptsTranscription Factor Binding SitesAID-induced lesionsNon-Ig genesGenome instabilityTranscription factorsAberrant targetingSequence dataCertain genesGenesAID targetingGerminal center B cellsSomatic mutationsLikely targetBinding sitesAID targetsTargetingClassification tree modelMistargetingB cellsLociMechanismTargetMutationsSites