The human fetal lymphocyte lineage: identification by CD27 and LIN28B expression in B cell progenitors

[摘要] CD27,amemberoftheTNFRsuperfamily,isusedtoidentifyhumanmemoryBcells.Nonetheless,CD27+BcellsarepresentinpatientswithHIGM1syndromewhoareunabletogenerateGCsormemoryBcells.CD27+IgD+fetalBcellsarepresentinumbilicalcordblood,andCD27mayalsobeamarkerofthehumanB1‐likeBcells.TodefinetheoriginofnaïveCD27+IgD+humanBcells,westudiedBcelldevelopmentinbothfetalandadulttissues.InhumanFL,mostCD19+cellscoexpressedCD10,amarkerofhumandevelopingBcells.SomeCD19+CD10+BcellsexpressedCD27,andthesefetalCD27+cellswerepresentinthepro‐B,pre‐B,andimmature/transitionalBcellcompartments.LowerfrequenciesofphenotypicallyidenticalcellswerealsoidentifiedinadultBM.CD27+pro‐B,pre‐B,andimmature/transitionalBcellsexpressedrecombinationactivatinggene‐1,terminaldeoxynucleotidyltransferaseandVpre‐BmRNAcomparablytotheirCD27−counterparts.CD27+andCD27−developingBcellsshowedsimilarIgheavychaingeneusagewithlowlevelsofmutations,suggestingthatCD27+developingBcellsaredistinctfrommutatedmemoryBcells.Despitethesesimilarities,CD27+developingBcellsdifferedfromCD27−developingBcellsbytheirincreasedexpressionofLIN28B,atranscriptionfactorassociatedwiththefetallymphoidlineagesofmice.Furthermore,CD27+pro‐BcellsefficientlygeneratedIgM+IgD+immature/transitionalBcellsinvitro.OurobservationssuggestthatCD27expressionduringBcelldevelopmentidentifiesaphysiologicstateorlineageforhumanBcelldevelopmentdistinctfromthememoryBcellcompartment...

[学科分类] 生理学

[关键词] human fetal liver;B cell development