Dicer ablation affects antibody diversity and cell survival in the B lymphocyte lineage

被引：484

作者：

Koralov, Sergei B. ^{[1
,2
]}

Muljo, Stefan A. ^{[1
,2
]}

Galler, Gunther R. ^{[1
,2
]}

Krek, Azra ^{[3
,4
]}

Chakraborty, Tirtha ^{[1
,2
]}

Kanellopoulou, Chryssa ^{[5
]}

Jensen, Kari ^{[1
,2
]}

Cobb, Bradley S. ^{[6
]}

Merkenschlager, Matthias ^{[6
]}

Rajewsky, Nikolaus ^{[3
]}

Rajewsky, Klaus ^{[1
,2
]}

机构：

[1] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA

[2] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA

[3] Max Delbruck Ctr Mol Med, D-13092 Berlin, Germany

[4] NYU, Dept Phys, New York, NY 10003 USA

[5] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA

[6] Univ London Imperial Coll Sci Technol & Med, Lymphocyte Dev Grp, MRC, Ctr Clin Sci, London W12 0NN, England

来源：

CELL | 2008年 / 132卷 / 05期

基金：

英国医学研究理事会;

关键词：

D O I：

10.1016/j.cell.2008.02.020

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

To explore the role of Dicer-dependent control mechanisms in B lymphocyte development, we ablated this enzyme in early B cell progenitors. This resulted in a developmental block at the pro- to pre-B cell transition. Gene-expression profiling revealed a miR-17 similar to 92 signature in the 3'UTRs of genes upregulated in Dicer-deficient pro-B cells; a top miR-17 similar to 92 target, the proapoptotic molecule Bim, was highly upregulated. Accordingly, B cell development could be partially rescued by ablation of Bim or transgenic expression of the prosurvival protein Bcl-2. This allowed us to assess the impact of Dicer deficiency on the V(D)J recombination program in developing B cells. We found intact Ig gene rearrangements in immunoglobulin heavy (IgH) and kappa chain loci, but increased sterile transcription and usage of D-H elements of the DSP family in IgH, and increased N sequence addition in Ig kappa due to deregulated transcription of the terminal deoxynucleotidyl transferase gene.

引用

页码：860 / 874

页数：15

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