Normal B cell precursors responsive to recombinant murine IL-7 and inhibition of IL-7 activity by transforming growth factor-beta.
Normal B cell precursors responsive to recombinant murine IL-7 and inhibition of IL-7 activity by transforming growth factor-beta.
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DOI：
10.4049/jimmunol.142.11.3875
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发表时间：
1989-06
影响因子：
4.4
通讯作者：
G. Lee;A. Namen;S. Gillis;L. Ellingsworth;P. Kincade
中科院分区：
文献类型：
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作者：
G. Lee;A. Namen;S. Gillis;L. Ellingsworth;P. Kincade
骨髓中基质细胞支持 B 淋巴细胞生成的能力可能部分是由生物活性因子的分泌介导的。第一个从基质细胞中分子克隆的具有淋巴细胞生成活性的细胞因子 IL-7，最初是通过其对长期培养的淋巴细胞的生长促进活性而被鉴定的。我们现在报道，鼠 rIL-7 是从新鲜骨髓中分离出的 B 细胞祖细胞的有效增殖刺激剂。增殖最初在具有B谱系相关Ag、Ly5/220和BP1的大前体细胞中最为明显。其中大部分还含有细胞质 Ig mu H 链。使用IL-7的扩展培养导致未成熟的c mu淋巴细胞占优势。没有观察到IL-7对成熟淋巴细胞的增殖有影响。它也不会诱导许多早期 B 谱系细胞系的成熟，也不会促进前体细胞形成 LPS 反应性、可克隆的 B 细胞。当掺入半固体琼脂培养基时，IL-7 特异性且快速地诱导前 B 细胞集落的形成，其相对于纯化的 B 细胞祖细胞制剂或未分级骨髓培养的细胞数量呈线性。在液体和琼脂培养条件下，IL-7 增殖活性可被两种相关形式的转化生长因子 (TGF) β（TGF-β 1 和 TGF-β 2）抑制。总而言之，这些结果表明 IL-7 是正常 B 谱系细胞在分化早期复制的刺激物，并且其活性可以通过其他细胞因子调节。 IL-7 还提供了一种研究单个 B 细胞祖代的后代以及在骨髓中其他细胞类型不形成集落的情况下计数可克隆前 B 细胞的方法。
The ability of stromal cells in bone marrow to support B lymphopoiesis may be partially mediated by secretion of biologically active factors. The first cytokine with lymphopoietic activity to be molecularly cloned from stromal cells, IL-7, was originally identified by its growth-promoting activity on long term cultured lymphocytes. We now report that murine rIL-7 is a potent proliferative stimulus for B cell progenitors isolated from fresh bone marrow. Proliferation was initially most obvious among large precursor cells which bear the B lineage associated Ag, Ly5/220 and BP1. A majority of these also contained cytoplasmic Ig mu H chains. Extended culture with IL-7 resulted in a predominance of immature c mu- lymphocytes. No effect by IL-7 was observed on the proliferation of mature lymphocytes. It also did not induce maturation in a number of early B lineage cell lines, or promote the formation of LPS-responsive, clonable B cells from precursors. When incorporated into semisolid agar medium, IL-7 specifically and rapidly induced the formation of pre-B cell colonies in a linear fashion with respect to numbers of cells cultured from either purified B cell progenitor preparations or unfractionated bone marrow. In both liquid and agar culture conditions, the IL-7 proliferative activity was inhibitable by two related forms of transforming growth factor (TGF) beta, TGF-beta 1 and TGF-beta 2. Taken together, these results indicate that IL-7 is a stimulus for replication of normal B lineage cells at an early stage of differentiation, and its activity can be modulated by other cytokines. IL-7 also provides a means of studying the progeny of a single B cell progenitor, and of enumerating clonable pre-B cells in the absence of colony formation by other cell types in bone marrow.