Deletion of Notch1 Converts Pro-T Cells to Dendritic Cells and Promotes Thymic B Cells by Cell-Extrinsic and Cell-intrinsic Mechanisms

被引：134

作者：

Feyerabend, Thorsten B. ^{[1
]}

Terszowski, Grzegorz ^{[1
]}

Tietz, Annette ^{[1
]}

Blum, Carmen ^{[1
]}

Luche, Herve ^{[1
]}

Gossler, Achim ^{[2
]}

Gale, Nicholas W. ^{[3
]}

Radtke, Freddy ^{[4
]}

Fehling, Hans Joerg ^{[1
]}

Rodewald, Hans-Reimer ^{[1
]}

机构：

[1] Univ Ulm, Inst Immunol, D-89081 Ulm, Germany

[2] Hannover Med Sch, Inst Mol Biol, D-30625 Hannover, Germany

[3] Regeneron Pharmaceut Inc, Tarrytown, NY 10591 USA

[4] Swiss Inst Expt Canc Res, Ecole Polytech Fed Lausanne, CH-1066 Epalinges, Switzerland

来源：

IMMUNITY | 2009年 / 30卷 / 01期

关键词：

LYMPHOCYTE DEVELOPMENT; LINEAGE DECISION; TRANSCRIPTION FACTORS; CARBOXYPEPTIDASE-A; ALPHA-BETA; IN-VIVO; PROGENITORS; FATE; GENE; PRECURSORS;

D O I：

10.1016/j.immuni.2008.10.016

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Notch1 signaling is required for T cell development and has been implicated in fate decisions in the thymus. We showed that Notch1 deletion in progenitor T cells (pro-T cells) revealed their latent developmental potential toward becoming conventional and plasmacytoid dendritic cells. In addition, Notch1 deletion in pro-T cells resulted in large numbers of thymic B cells, previously explained by T-to-B cell fate conversion. Single-cell genotyping showed, however, that the majority of these thymic B cells arose from Notch1-sufficient cells by a cell-extrinsic pathway. Fate switching nevertheless exists for a subset of thymic B cells originating from Notch1 deleted pro-T cells. Chimeric mice lacking the Notch ligand delta-like 4 (DII4) in thymus epithelium revealed an essential role for DII4 in T cell development. Thus, Notch1-DII4 signaling fortifies T cell commitment by suppressing non-T cell lineage potential in pro-T cells, and normal Notch1-driven T cell development repels excessive B cells in the thymus.

引用

页码：67 / 79

页数：13

共 61 条

[11] Maintenance of somite borders in mice requires the Delta homologue DII1 [J].