B-Cell Lymphopoiesis Is Regulated by Cathepsin L.docVIP

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B-Cell Lymphopoiesis Is Regulated by Cathepsin L.doc

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B-Cell Lymphopoiesis Is Regulated by Cathepsin L

B-CellLymphopoiesisIsRegulatedbyCathepsinL MariaNoelBadano1,GabrielaLorenaCamicia1,GabrielaLombardi2,AndreaMaglioco1, GabrielCabrera1,HectorCosta1,RobertoPabloMeiss3,IsabelPiazzon1.,IreneNepomnaschy1*. 1Laboratorio de Inmunolog?′a Experimental, Instituto de Medicina Experimental-Consejo Nacional de Investigaciones Cient?′ficas y Te′cnicas, Academia Nacional de Medicina,BuenosAires,Argentina,2LaboratoriodeInmunofarmacolog?′aTumoral,CentrodeEstudiosFarmacolo′gicosyBota′nicos, ConsejoNacionaldeInvestigaciones Cient?′ficasyTe′cnicas,FacultaddeMedicina,UniversidaddeBuenosAires,BuenosAires,Argentina,3CentrodeEstudiosOncolo′gicos,AcademiaNacionaldeMedicina, BuenosAires,Argentina Abstract CathepsinL(CTSL)isaubiquitouslyexpressedlysosomalcysteinepeptidasewithdiverseandhighlyspecificfunctions.The involvementofCTSLinthymicCD4+T-cellpositiveselectionhasbeenwelldocumented.UsingCTSLnkt/nkt micethatlack CTSLactivity,wehavepreviouslydemonstratedthattheabsenceofCTSLactivityaffectsthehomeostasisoftheT-cellpool by decreasing CD4+ cell thymic production and increasing CD8+ thymocyte production. Herein we investigated the influenceofCTSLactivityonthehomeostasisofperipheralB-cellpopulationsandbonemarrow(BM)B-cellmaturation.B- cell numbers were increased in lymph nodes (LN), spleen and blood from CTSLnkt/nkt mice. Increases in splenic B-cell numberswererestrictedtotransitionalT1andT2cellsandtothemarginalzone(MZ)cellsubpopulation.Noalterationsin the proliferative or apoptosis levels were detected in peripheral B-cell populations from CTSLnkt/nkt mice. In the BM, the percentageandtheabsolutenumberofpre-pro-B,pro-B,pre-B,immatureandmatureBcellswerenotaltered.However,in vitroandinvivoexperimentsshowedthatBMB-cellproductionwasmarkedlyincreasedinCTSLnkt/nkt mice.Besides,BMB- cellemigrationtothespleenwasincreasedinCTSLnkt/nktmice.Colony-formingunitpre-B(CFUpre-B)assaysinthepresence ofBMstromalcells(SC)andreciprocalBMchimerasrevealedthatbothBMB-cellprecursorsandSCwouldcontrib