Development of immunoglobulin λ-chain-positive B cells, but not editing of immunoglobulin κ-chain, depends on NF-κB signals

被引：72

作者：

Derudder, Emmanuel ^{[1
]}

Cadera, Emily J. ^{[2
]}

Vahl, J. Christoph ^{[1
,3
]}

Wang, Jing ^{[1
]}

Fox, Casey J. ^{[4
]}

Zha, Shan ^{[5
]}

van Loo, Geert ^{[6
,7
]}

Pasparakis, Manolis ^{[8
,9
]}

Schlissel, Mark S. ^{[2
]}

Schmidt-Supprian, Marc ^{[1
,3
]}

Rajewsky, Klaus ^{[1
]}

机构：

[1] Immune Dis Inst, Boston, MA USA

[2] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA

[3] Max Planck Inst Biochem, D-82152 Martinsried, Germany

[4] Jackson Lab, Bar Harbor, ME 04609 USA

[5] Harvard Univ, Sch Med, Howard Hughes Med Inst, Childrens Hosp,Immune Dis Inst,Dept Genet, Boston, MA 02115 USA

[6] VIB, Dept Mol Biomed Res, Ghent, Belgium

[7] Univ Ghent, B-9000 Ghent, Belgium

[8] Univ Cologne, Inst Genet, Ctr Mol Med, D-5000 Cologne, Germany

[9] Univ Cologne, Cologne Excellence Cluster Cellular Stress Respon, D-5000 Cologne, Germany

来源：

NATURE IMMUNOLOGY | 2009年 / 10卷 / 06期

基金：

美国国家卫生研究院;

关键词：

LYMPHOCYTE DEVELOPMENT; RECEPTOR SIGNALS; TRANSCRIPTION; REARRANGEMENT; EXPRESSION; PROMOTES; MICE; TOLERANCE; SUPPRESSION; GENERATION;

D O I：

10.1038/ni.1732

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

071005 [微生物学]; 100108 [医学免疫学];

摘要：

By genetically ablating I kappa B kinase (IKK)-mediated activation of the transcription factor NF-kappa B in the B cell lineage and by analyzing a mouse mutant in which immunoglobulin lambda-chain-positive B cells are generated in the absence of rearrangements in the locus encoding immunoglobulin kappa-chain, we define here two distinct, consecutive phases of early B cell development that differ in their dependence on IKK-mediated NF-kappa B signaling. During the first phase, in which NF-kappa B signaling is dispensable, predominantly kappa-chain-positive B cells are generated, which undergo efficient receptor editing. In the second phase, predominantly lambda-chain-positive B cells are generated whose development is ontogenetically timed to occur after rearrangements of the locus encoding kappa-chain. This second phase of development is dependent on NF-kappa B signals, which can be substituted by transgenic expression of the prosurvival factor Bcl-2.

引用

页码：647 / U118

页数：9

共 49 条

[1]

An immunoglobulin Cκ-reactive single chain antibody fusion protein induces tolerance through receptor editing in a normal polyclonal immune system [J].