Thymic stromal lymphopoietin induces early human B-cell proliferation and differentiation
Thymic stromal lymphopoietin induces early human B-cell proliferation and differentiation
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DOI：
10.1002/eji.200939419
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发表时间：
2010-04-01
影响因子：
5.4
通讯作者：
Blom, Bianca
中科院分区：
文献类型：
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作者：
Scheeren, Ferenc A.;van Lent, Anja U.;Blom, Bianca
胸腺基质淋巴细胞生成素（TSLP）是一种结合IL-7受体-α链和独特TSLP受体（TSLPR）链的细胞因子。TSLP在人类B细胞发育中的作用尚未阐明。我们发现TSLPR转录本在来自胎肝和骨髓的CD 34（+）细胞中表达最显著。在一般情况下，TSLPR的细胞表面表达是低的，除了在一个子集的多系提交的祖细胞。TSLP可诱导STAT 5酪氨酸磷酸化，促进多系分化的祖细胞、前B细胞和前B细胞的增殖。与IL-7相比，TSLP刺激后B细胞祖细胞的增殖水平较低。胎儿细胞表面BCR的表达与TSLP或IL-7反应性呈负相关。来自胎儿骨髓的前B细胞，而不是胎儿肝脏，对TSLP或IL-7刺激无效。当采用从CD 34（+）CD 38（-）多能HSC开始的体外B细胞分化培养系统时，IL-7诱导前体细胞扩增的短波，但不导致成熟B细胞的长期存活。TSLP能够增加更成熟的人B细胞的比例和绝对数。总之，我们提供的证据表明TSLP支持胎儿造血祖细胞的人B细胞分化。
Thymic stromal lymphopoietin (TSLP) is a cytokine that binds the IL-7-receptor-alpha chain and a unique TSLP receptor (TSLPR) chain. The role of TSLP in human B-cell development has not been elucidated. We show that TSLPR transcripts are expressed most prominently in CD34(+) cells from fetal liver and BM. In general, cell surface expression of TSLPR was low, except on a subset of multilineage-commited progenitor cells. TSLP induced the tyrosine-phosphorylation of STAT5 and the proliferation of multilineage-commited progenitor cells, pro-B cells and pre-B cells. Compared with IL-7, the levels of proliferation after stimulation of the B-cell progenitors with TSLP were lower. Expression of the BCR on the cell surface of fetal cells was inversely correlated to TSLP or IL-7 responsiveness. Pre-B cells from fetal BM, but not fetal liver, were refractory to TSLP or IL-7 stimulation. When employing an in vitro B-cell differentiation culture system starting from CD34(+)CD38(-) multipotent HSC, IL-7 induced a short wave of precursor cell expansion but did not result in long-term survival of mature B cells. TSLP was capable of increasing the proportion and the absolute numbers of more mature human B cells. Overall, we provide evidence that TSLP supports human B-cell differentiation from fetal hematopoietic progenitors.