Antigen-Engaged B Cells Undergo Chemotaxis toward the T Zone and Form Motile Conjugates with Helper T Cells.docVIP

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Antigen-Engaged B Cells Undergo Chemotaxis toward the T Zone and Form Motile Conjugates with Helper T Cells.doc

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Antigen-Engaged B Cells Undergo Chemotaxis toward the T Zone and Form Motile Conjugates with Helper T Cells

o Openaccess,freelyavailableonline PL S BIOLOGY Antigen-EngagedBCellsUndergoChemotaxis towardtheTZoneandFormMotileConjugates withHelperTCells Takaharu Okada1[,Mark J.Miller2[¤a,Ian Parker3,Matthew F.Krummel4,Margaret Neighbors5¤b, Suzanne B.Hartley5¤c,Anne O’Garra5¤d,Michael D.Cahalan2*,Jason G.Cyster1* 1Howard Hughes Medical Institute and Department of Microbiology and Immunology, University of California, San Francisco, California, United States of America, 2DepartmentofPhysiologyandBiophysics,UniversityofCalifornia,Irvine,California,UnitedStatesofAmerica,3DepartmentofNeurobiologyandBehavior,Universityof California,Irvine,California,UnitedStatesofAmerica, 4DepartmentofPathology,UniversityofCalifornia,SanFrancisco,California,UnitedStatesofAmerica,5Department ofImmunobiology,DNAXResearchInstitute,PaloAlto,California,UnitedStatesofAmerica InteractionsbetweenBandTcellsareessentialformostantibodyresponses,butthedynamicsoftheseinteractions arepoorlyunderstood.Bytwo-photonmicroscopyofintactlymphnodes,weshowthatuponexposuretoantigen,B cellsmigratewithdirectionalpreferencetowardtheB-zone–T-zoneboundaryinaCCR7-dependentmanner,througha region that exhibits a CCR7-ligand gradient. Initially the B cells show reduced motility, but after 1 d, motility is increasedtoapproximately9lm/min.Antigen-engagedBcellspairwithantigen-specifichelperTcellsfor10tomore than 60 min, whereas non-antigen-specific interactions last less than 10 min. B cell–T cell conjugates are highly dynamicandmigrateextensively,beingledbyBcells.BcellsoccasionallycontactmorethanoneTcell,whereasTcells arestrictlymonogamousintheirinteractions.Thesefindingsprovideevidenceoflymphocytechemotaxisinvivo,and theybegintodefinethespatiotemporalcellulardynamicsassociatedwithTcell–dependentantibodyresponses. Citation:OkadaT,MillerMJ,ParkerI,KrummelMF,NeighborsM,etal.(2005)Antigen-engagedBcellsundergochemotaxistowardtheTzoneandformmotileconjugates withhelperTcells.PLoSBiol3(6):e150. spleenandlymphnodesections[7,8].