Antibody Vh Repertoire Differences between Resolving and Chronically Evolving Hepatitis C Virus Infections 英文参考文献.docVIP

AntibodyVhRepertoireDifferencesbetweenResolving andChronicallyEvolvingHepatitisCVirusInfections VitoRacanelli1*,ClaudiaBrunetti1,ValliDeRe2,LauraCaggiari2,MariangelaDeZorzi2,PatriziaLeone1, FedericoPerosa1,AngeloVacca1,FrancoDammacco1 1Department of Internal Medicine and Clinical Oncology, University of Bari Medical School, Bari, Italy, 2Experimental and Clinical Pharmacology Unit, Centro di RiferimentoOncologico,IRCCSNationalCancerInstitute,Aviano(PN),Italy Abstract DespitetheproductionofneutralizingantibodiestohepatitisCvirus(HCV),manypatientsfailtoclearthevirusandinstead developchronicinfectionandlong-termcomplications.TounderstandhowHCVinfectionperturbstheantibodyrepertoire and to identify molecular features of antibody genes associated with either viral clearance or chronic infection, we sequencedtheV(D)Jregionofna?¨veandmemoryBcellsof6personswhospontaneouslyresolvedanHCVinfection(SR),9 patientswithanewlydiagnosedchronicallyevolvinginfection(CE),and7healthydonors.Inbothna?¨veandmemoryBcells, the frequency of use of particular antibody gene subfamilies and segments varied among the three clinical groups, especiallybetweenSRandCE.ComparedtoCE,SRantibodygenesusedfewerVH,DandJHgenesegmentsinna?¨veBcells and fewer VH segments in memory B cells. SR and CE groups significantly differed in the frequency of use of 7 gene segmentsinna?¨veBcellclonesand3genesegmentsinmemoryclones.Thenucleotidemutationratesweresimilaramong groups,butthepatternofreplacementandsilentmutationsinmemoryBcellclonesindicatedgreaterantigenselectionin SRthanCE.GreaterclonalevolutionofSRthanCEmemoryBcellswasrevealedbyanalysisofphylogenetictreesandCDR3 lengths.PauciclonalityoftheperipheralmemoryBcellpopulationisadistinguishingfeatureofpersonswhospontaneously resolved an HCV infection. This finding, previously considered characteristic only of patients with HCV-associated lymphoproliferativedisorders,suggeststhattheBcellclonespotentiallyinvolvedinclearanceofthevirusmayalsobethose susceptibletoabnorm