Basal Immunoglobulin Signaling Actively Maintains Developmental Stage in Immature B Cells.docVIP

下载本文档

4
0
约6.92万字
约 13页
2017-05-07 发布于上海
举报
版权申诉

Basal Immunoglobulin Signaling Actively Maintains Developmental Stage in Immature B Cells.doc

1、本文档共13页，可阅读全部内容。
2、原创力文档（book118）网站文档一经付费（服务费），不意味着购买了该文档的版权，仅供个人/单位学习、研究之用，不得用于商业用途，未经授权，严禁复制、发行、汇编、翻译或者网络传播等，侵权必究。
3、本站所有内容均由合作方或网友上传，本站不对文档的完整性、权威性及其观点立场正确性做任何保证或承诺！文档内容仅供研究参考，付费前请自行鉴别。如您付费，意味着您自己接受本站规则且自行承担风险，本站不退款、不进行额外附加服务；查看《如何避免下载的几个坑》。如果您已付费下载过本站文档，您可以点击这里二次下载。
4、如文档侵犯商业秘密、侵犯著作权、侵犯人身权等，请点击“版权申诉”（推荐），也可以打举报电话：400-050-0827(电话支持时间：9:00-18:30)。
5、该文档为VIP文档，如果想要下载，成为VIP会员后，下载免费。
6、成为VIP后，下载本文档将扣除1次下载权益。下载后，不支持退款、换文档。如有疑问请联系我们。
7、成为VIP后，您将拥有八大权益，权益包括：VIP文档下载权益、阅读免打扰、文档格式转换、高级专利检索、专属身份标志、高级客服、多端互通、版权登记。
8、VIP文档为合作方或网友上传，每下载1次，网站将根据用户上传文档的质量评分、类型等，对文档贡献者给予高额补贴、流量扶持。如果你也想贡献VIP文档。上传文档

Basal Immunoglobulin Signaling Actively Maintains Developmental Stage in Immature B Cells

o Openaccess,freelyavailableonline PL S BIOLOGY BasalImmunoglobulinSignaling ActivelyMaintainsDevelopmentalStage inImmatureBCells Lina E.Tze1¤,Brian R.Schram1,Kong-Peng Lam2,Kristin A.Hogquist1,Keli L.Hippen1,Jiabin Liu1,Susan A.Shinton3, Kevin L.Otipoby4,Peter R.Rodine1,Amanda L.Vegoe1,Manfred Kraus4,Richard R.Hardy3,Mark S.Schlissel5, Klaus Rajewsky4,Timothy W. Behrens1* 1CenterforImmunology,UniversityofMinnesotaMedicalSchool,Minneapolis,Minnesota,UnitedStatesofAmerica,2InstituteofMolecularandCellBiology,Singapore, 3FoxChaseCancerCenter,Philadelphia,Pennsylvania,UnitedStatesofAmerica,4CenterforBloodResearch,HarvardMedicalSchool,Boston,Massachusetts,UnitedStates ofAmerica,5DepartmentofMolecularandCellBiology,UniversityofCalifornia,Berkeley,California,UnitedStatesofAmerica IndevelopingBlymphocytes,asuccessfulV(D)Jheavychain(HC)immunoglobulin(Ig)rearrangementestablishesHC allelicexclusionandsignalspro-Bcellstoadvanceindevelopmenttothepre-Bstage.Asubsequentfunctionallight chain(LC)rearrangementthenresultsinthesurfaceexpressionofIgMattheimmatureBcellstage.Hereweshowthat interruptionofbasalIgMsignalinginimmatureBcells,eitherbytheinducibledeletionofsurfaceIgviaCre-mediated excision or by incubating cells with the tyrosine kinase inhibitor herbimycin A or the phosphatidylinositol 3-kinase inhibitor wortmannin, led to a striking ‘‘back-differentiation’’ of cells to an earlier stage in B cell development, characterized by the expression of pro-B cell genes. Cells undergoing this reversal in development also showed evidenceofnewLCgenerearrangements,suggestinganimportantroleforbasalIgsignalinginthemaintenanceofLC allelic exclusion. These studies identify a previously unappreciated level of plasticity in the B cell developmental program,andhaveimportantimplicationsforourunderstandingofcentraltolerancemechanisms. Citation: TzeLE, SchramBR,LamKP, HogquistKA,Hippen KL,et al.(2005)Basalimmunoglobulinsignalingactivelymaintains developmentalstageinimmature Bcells