CD19-independent instruction of murine marginal zone B-cell development by constitutive Notch2 signaling
CD19-independent instruction of murine marginal zone B-cell development by constitutive Notch2 signaling
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DOI：
10.1182/blood-2010-12-325944
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发表时间：
2011-12-08
期刊：
影响因子：
20.3
通讯作者：
Zimber-Strobl, Ursula
中科院分区：
文献类型：
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作者：
Hampel, Franziska;Ehrenberg, Stefanie;Zimber-Strobl, Ursula
B细胞特异性基因Notch2的消融导致边缘区（MZ） B细胞谱系的缺失。为了分析构成型Notch2信号在B细胞中的作用，我们产生了一种转基因小鼠品系，该品系允许有条件地表达构成型活性的细胞内Notch2 （Notch2IC）。在b细胞谱系的早期发育阶段，Notch2IC的表达完全消除了b细胞的产生，并导致骨髓中异位T细胞的发育（BM），这表明Notch2IC与Notch1IC在驱动异位T细胞分化中起冗余作用。在明确致力于B细胞谱系的B细胞中，Notch2IC诱导所有细胞向MZ B细胞区区移动，牺牲滤泡B细胞。表达notch2ic的B细胞定位于MZ，表达特征表面标记物，刺激后增殖增强，Akt、Erk和Jnk基础活性增加，反映了野生型MZ B细胞的表型。即使在缺乏CD19的情况下，也可以在脾脏中实现notch2ic驱动的MZ b细胞生成。我们的研究结果表明，过渡型1 B细胞中的构成型Notch2信号足以驱动MZ B细胞分化。(血。2011;118 (24):6321 - 6331)
B cell-specific gene ablation of Notch2 results in the loss of the marginal zone (MZ) B-cell lineage. To analyze the effects of constitutive Notch2 signaling in B cells, we have generated a transgenic mouse strain that allows the conditional expression of a constitutively active, intracellular form of Notch2 (Notch2IC). Expression of Notch2IC at the earliest developmental stages of the B-cell lineage completely abolished B-cell generation and led to the development of ectopic T cells in the bone marrow (BM), showing that Notch2IC is acting redundantly with Notch1IC in driving ectopic T-cell differentiation. In B cells clearly committed to the B-cell lineage induction of Notch2IC drove all cells toward the MZ B-cell compartment at the expense of follicular B cells. Notch2IC-expressing B cells reflected the phenotype of wild-type MZ B cells for their localization in the MZ, the expression of characteristic surface markers, their enhanced proliferation after stimulation, and increased basal activity of Akt, Erk, and Jnk. Notch2IC-driven MZ B-cell generation in the spleen was achieved even in the absence of CD19. Our results implicate that a constitutive Notch2 signal in transitional type 1 B cells is sufficient to drive MZ B-cell differentiation. (Blood. 2011;118(24):6321-6331)