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条件性PU.1基因敲除小鼠中功能性B淋巴细胞的发育

The development of functional B lymphocytes in conditional PU.1 knock-out mice.

作者信息

Polli Matthew, Dakic Aleksandar, Light Amanda, Wu Li, Tarlinton David M, Nutt Stephen L

机构信息

The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria, Australia 3050.

出版信息

Blood. 2005 Sep 15;106(6):2083-90. doi: 10.1182/blood-2005-01-0283. Epub 2005 Jun 2.

Abstract

An abundance of research has entrenched the view that the Ets domain containing transcription factor PU.1 is fundamental to the development and function of B lymphocytes. In this study, we have made use of a conditional PU.1 allele to test this notion. Complete deletion of PU.1 resulted in the loss of B cells and all other lineage-positive cells in the fetal liver and death between E18.5 and birth; however, specific deletion of PU.1 in the B lineage had no effect on B-cell development. Furthermore, deletion of PU.1 in B cells did not compromise their ability to establish and maintain an immune response. An increased level of apoptosis was observed in vitro upon B-cell receptor (BCR) cross-linking; however, this was partially rescued by interleukin-4 (IL-4). These findings suggest that PU.1 is not essential for the development of functional B lymphocytes beyond the pre-B stage.

摘要

大量研究巩固了这样一种观点,即含有Ets结构域的转录因子PU.1对B淋巴细胞的发育和功能至关重要。在本研究中,我们利用了一个条件性PU.1等位基因来验证这一观点。PU.1的完全缺失导致胎肝中B细胞和所有其他谱系阳性细胞的丧失,并在E18.5至出生之间死亡;然而,B谱系中PU.1的特异性缺失对B细胞发育没有影响。此外,B细胞中PU.1的缺失并不损害它们建立和维持免疫反应的能力。在体外,B细胞受体(BCR)交联后观察到凋亡水平增加;然而,白细胞介素-4(IL-4)部分挽救了这种情况。这些发现表明,PU.1对于前B阶段之后功能性B淋巴细胞的发育并非必不可少。

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