Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society | |
Genetic and cellular dissection of the activation of AM14 rheumatoid factor B cells in a mouse model of lupus | |
关键词: autoantibody; B cell tolerance; autoimmunity; BCR transgenic mice; | |
DOI : 10.1189/jlb.1A1214-576R | |
学科分类:生理学 | |
来源: Federation of American Societies for Experimental Biology | |
【 摘 要 】
TheRF‐specificAM14tgBCRhasbeenusedasamodeltodissectthemechanismsofBcelltolerancetoICscontainingnucleicacids.WehaveshownpreviouslythatAM14RFBcellsbreaktoleranceintheTCmousemodeloflupusthroughthedualengagementoftheAM14BCRandTLR9.Inthisstudy,weshowedthatneithertheexpressionofSle1orSle2susceptibilitylocialonewassufficienttoactivateAM14RFBcells,suggestingthattheproductionofantichromatinIgG2aaautoAgmediatedbySle1andanintrinsicallyhigherBcellactivationmediatedbySle2wererequired.WealsoshowedthattheB6geneticbackgroundenhancedtheselectionofAM14RFBcellstotheMZBcellcompartmentregardlessoftheexpressionoftheSlelociandtherefore,oftheiractivationintoAFCs.Furthermore,someAM14RFBcellswereselectedintotheB‐1acompartment,wheretheydidnotdifferentiateintoAFCs.Therefore,itisunlikelythattheselectionofAM14RFBcellstotheMZBorB‐1acellcompartmentsinTC.AM14amiceisresponsiblefortheirbreachoftolerance.Finally,weshowedthatthepresenceofexpressionofSle1innon‐tgcells,mostlikelyTcells,isnecessaryfortheactivationofAM14RFBcellsintoAFCs.Overall,theseresultssuggestathresholdmodelofactivationofAM14RFBcellsontheB6backgroundwithadditivegeneticandcellularcontributionofmultiplesources...
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