Differential regulation of mouse B cell development by transforming growth factor beta1.
Differential regulation of mouse B cell development by transforming growth factor beta1.
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DOI：
10.1080/1044667031000088057
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发表时间：
2002-06
期刊：
影响因子：
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通讯作者：
Burrows, Peter D
中科院分区：
文献类型：
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作者：
Kaminski, Denise A;Letterio, John J;Burrows, Peter D
转化生长因子β（Transforming growth factor β，TGFβ）可抑制B祖细胞、成熟B淋巴细胞和浆细胞的体外增殖、存活和分化。在这里，我们证明了TGFβ1-/-小鼠骨髓（BM）B祖细胞和未成熟B细胞的意外的、年龄依赖性的减少。为了评估正常B谱系发育期间的TGFβ反应性，将细胞在白细胞介素7（IL 7）±TGFβ中培养。皮摩尔剂量的TGFβ1在每个时间点降低了前B细胞的回收率。相比之下，前B细胞的数量最初减少，但随后与单独的IL 7相比增加，导致前B细胞群的生长速率增加4倍。纯化的BM亚群分析表明，pro-B细胞和最早的BP 1- pre-B细胞对TGFβ1的抑制作用敏感。然而，大的BP 1+前B细胞，虽然最初减少，但在培养的第5天和第7天数量增加。这些结果表明，TGFβ1对体内正常B细胞发育是重要的，并且B细胞祖细胞根据其分化阶段受到细胞因子的不同影响。
Transforming growth factor β (TGFβ) can inhibit the in vitro proliferation, survival and differentiation of B cell progenitors, mature B lymphocytes and plasma cells. Here we demonstrate unexpected, age-dependent reductions in the bone marrow (BM) B cell progenitors and immature B cells in TGFβ1-/- mice. To evaluate TGFβ responsiveness during normal B lineage development, cells were cultured in interleukin 7 (IL7)±TGFβ. Picomolar doses of TGFβ1 reduced pro-B cell recoveries at every timepoint. By contrast, the pre-B cells were initially reduced in number, but subsequently increased compared to IL7 alone, resulting in a 4-fold increase in the growth rate for the pre-B cell population. Analysis of purified BM sub-populations indicated that pro-B cells and the earliest BP1- pre-B cells were sensitive to the inhibitory effects of TGFβ1. However, the large BP1+ pre-B cells, although initially reduced, were increased in number at days 5 and 7 of culture. These results indicate that TGFβ1 is important for normal B cell development in vivo, and that B cell progenitors are differentially affected by the cytokine according to their stage of differentiation.