Division of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Eur J Immunol. 2010 Apr;40(4):955-65. doi: 10.1002/eji.200939419.
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.
胸腺基质淋巴细胞生成素 (TSLP) 是一种细胞因子，可与 IL-7 受体-α 链和独特的 TSLP 受体 (TSLPR) 链结合。TSLP 在人类 B 细胞发育中的作用尚未阐明。我们表明，TSLPR 转录本在胎肝和 BM 的 CD34(+)细胞中表达最为明显。一般来说，TSLPR 的细胞表面表达水平较低，除了在多谱系定向祖细胞亚群上。TSLP 诱导 STAT5 的酪氨酸磷酸化和多谱系定向祖细胞、前 B 细胞和前 B 细胞的增殖。与 IL-7 相比，TSLP 刺激 B 细胞祖细胞后的增殖水平较低。胎细胞表面 BCR 的表达与 TSLP 或 IL-7 反应性呈负相关。来自胎 BM 的前 B 细胞，但不是胎肝，对 TSLP 或 IL-7 刺激无反应。当采用从 CD34(+)CD38(-)多能 HSC 开始的体外 B 细胞分化培养系统时，IL-7 诱导了前体细胞的短暂扩张波，但不能导致成熟 B 细胞的长期存活。TSLP 能够增加更成熟的人类 B 细胞的比例和绝对数量。总体而言，我们提供的证据表明 TSLP 支持人类 B 细胞从胎血造血祖细胞分化。
