In vitro effects of recombinant interleukin 7 on growth and differentiation of bone marrow pro-B- and pro-T-lymphocyte clones and fetal thymocyte clones.
In vitro effects of recombinant interleukin 7 on growth and differentiation of bone marrow pro-B- and pro-T-lymphocyte clones and fetal thymocyte clones.
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重组白细胞介素 7 对骨髓前 B 淋巴细胞和前 T 淋巴细胞克隆以及胎儿胸腺细胞克隆的生长和分化的体外影响。
DOI：
10.1073/pnas.86.5.1634
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发表时间：
1989
影响因子：
11.1
通讯作者：
R. Palacios
中科院分区：
文献类型：
--
作者：
S. Takeda;S. Gillis;R. Palacios
研究了重组人白细胞介素7（IL-7）对骨髓前B淋巴细胞克隆生长和分化的影响（CB/Bm 7、LyD 9、LyB 9），骨髓前T淋巴细胞克隆（C4-77/3、C4-86/18、C4-95/16）和胎儿胸腺细胞克隆0.10的存在或不存在的情况下，将骨髓基质克隆RP.0.10（其因其促进pro-B克隆分化的能力而被选择）与前B克隆（FTH 5、FTA 2、FTD 5）进行比较。rIL-7单独刺激一些DNA合成（通过[3 H]胸苷摄取测量），但不刺激pro-B克隆的实际生长（细胞数量增加）。针对IL-4和IL-6或针对IL-2、IL-3和IL-5受体的抗体不抑制rIL-7对pro-B克隆的这种作用。单独的rIL-7或与其它细胞因子（从rIL-1 α到rIL-6）的各种组合不能诱导前B克隆分化为IgM+ B细胞，而不管是否存在脂多糖（LPS）。RP.0.10骨髓基质细胞本身并不支持pro-B克隆的生长。然而，当与rIL-7和单层RP. 0.10基质细胞一起培养时，pro-B克隆生长。当在LPS和rIL-3存在下培养时，RP. 0.10基质细胞诱导前B克隆分化为IgM+ B细胞而不是T3+ T细胞，而B细胞祖细胞克隆产生显著更高数量的IgM+ B细胞（高达63%），并且当与rIL-7、LPS和RP. 0.10基质细胞共培养时，更多的B细胞表达更高水平的表面IgM。当在不存在LPS的情况下与RP. 0.10基质细胞和rIL-7共培养时，前B克隆也产生IgM+ B细胞（高达20%）。通过使用设计用于测试细胞-细胞接触要求的培养板，我们发现，前B细胞和骨髓基质细胞之间的细胞相互作用对于诱导前B克隆中免疫球蛋白基因的重排和表达是必不可少的。RP.0.10基质细胞的存在下，对原B克隆的生长和分化的rIL-7的显着影响的可能机制进行了讨论。最后，rIL-7单独或与RP. 0.10基质细胞一起既不支持骨髓pro-T克隆或胎儿胸腺细胞克隆的增殖，也不诱导其分化为T3+ T细胞或IgM+ B细胞。根据这些发现，我们推测多能干细胞与骨髓基质细胞（如RP. 0. 10）的相互作用以及IL-7的可用性可能在B淋巴细胞途径沿着发育的承诺中发挥关键作用。
We have studied the effects of recombinant (r) interleukin 7 (IL-7) on growth and differentiation of marrow pro-B-lymphocyte clones (CB/Bm7, LyD9, LyB9), marrow pro-T-lymphocyte clones (C4-77/3, C4-86/18, C4-95/16), and fetal thymocyte clones (FTH5, FTA2, FTD5) in the presence or absence of the bone marrow stroma clone RP.0.10, which was selected for its ability to promote differentiation of the pro-B clones. rIL-7 alone stimulated some DNA synthesis (measured by [3H]thymidine uptake) but not actual growth (increase in cell number) of the pro-B clones. Antibodies against IL-4 and IL-6 or against receptors for IL-2, IL-3, and IL-5 did not inhibit this effect of rIL-7 on the pro-B clones. rIL-7 alone or in various combinations with other cytokines (from rIL-1 alpha to rIL-6) could not induce differentiation of the pro-B clones into IgM+ B cells regardless of the presence of lipopolysaccharide (LPS). The RP.0.10 marrow stroma cells by themselves do not support the growth of the pro-B clones. However, the pro-B clones grew when cultured with rIL-7 and monolayers of the RP.0.10 stroma cells. While the RP.0.10 stroma cells induced the pro-B clones to differentiate into IgM+ B cells but not T3+ T cells when cultured in the presence of LPS and rIL-3, the B-cell progenitor clones gave rise to significantly higher numbers of IgM+ B cells (up to 63%) and to many more B cells expressing higher levels of surface IgM when cocultured with rIL-7, LPS, and RP.0.10 stroma cells. The pro-B clones also generated IgM+ B cells (up to 20%) when cocultured with RP.0.10 stroma cells and rIL-7 in the absence of LPS. By using culture plates designed for testing requirements for cell-cell contact, we found that cell interactions between the pro-B cell and the marrow stroma cell are essential to induce rearrangement and expression of the immunoglobulin genes in the pro-B clones. Possible mechanisms to account for the remarkable effects of rIL-7 in the presence of RP.0.10 stroma cells on both growth and differentiation of the pro-B clones are discussed. Finally, rIL-7 alone or together with RP.0.10 stroma cells neither supported proliferation nor induced differentiation into T3+ T cells or IgM+ B cells of the marrow pro-T clones or the fetal thymocyte clones. In light of these findings, we postulate that the interaction of the pluripotential stem cell with marrow stroma cells like RP.0.10 and the availability of IL-7 could play a critical role in the commitment to develop along the B-lymphocyte pathway.