Ray R J, Furlonger C, Williams D E, Paige C J
Wellesley Hospital Research Institute, University of Toronto, Canada.
Eur J Immunol. 1996 Jan;26(1):10-6. doi: 10.1002/eji.1830260103.
B cell development is dependent on both direct interactions with stromal cells and their secreted cytokines. The precise mechanisms by which these interactions regulate B cell differentiation are currently unknown. We report here that a novel growth factor thymic stromal-derived lymphopoietin (TSLP) can replace the activity of interleukin-7 (IL-7) in supporting B cell development in vitro. TSLP was found to promote the proliferation and differentiation of committed B220+ B cell progenitors from day 15 fetal liver. Phenotypic analysis of these cells revealed that they are at the pro-B cell stage of differentiation and express cell surface markers characteristic of pro-B cells cultured in IL-7. TSLP can replace the activity of IL-7 in supporting the progression of B lymphocytes from uncommitted bipotential precursors. In the absence of either TSLP or IL-7, the progeny of cells that give rise to mature B lymphocytes fail to develop from these bipotential precursors. Moreover, TSLP can substitute for IL-7 in supporting the sustained proliferative response exhibited by B cell progenitors from CBA/N mice. Together these results show that TSLP can replace the requirement for IL-7 during in vitro B cell development.
B细胞的发育既依赖于与基质细胞的直接相互作用,也依赖于它们分泌的细胞因子。目前尚不清楚这些相互作用调节B细胞分化的确切机制。我们在此报告,一种新型生长因子胸腺基质衍生的淋巴细胞生成素(TSLP)在体外支持B细胞发育方面可以替代白细胞介素-7(IL-7)的活性。研究发现,TSLP能促进来自15日龄胎肝的定向B220+B细胞祖细胞的增殖和分化。对这些细胞的表型分析表明,它们处于B细胞分化的前B细胞阶段,并表达在IL-7中培养的前B细胞特有的细胞表面标志物。TSLP在支持B淋巴细胞从未定向双潜能前体进展方面可以替代IL-7的活性。在缺乏TSLP或IL-7的情况下,产生成熟B淋巴细胞的细胞后代无法从这些双潜能前体发育而来。此外,TSLP在支持CBA/N小鼠的B细胞祖细胞表现出的持续增殖反应方面可以替代IL-7。这些结果共同表明,在体外B细胞发育过程中,TSLP可以替代对IL-7的需求。