King A G, Wierda D, Landreth K S
Department of Pharmacology and Toxicology, West Virginia University Medical Center, Morgantown 26506.
J Immunol. 1988 Sep 15;141(6):2016-26.
Our experiments have addressed regulation of B lymphocyte formation by bone marrow stromal cells. Stromal cells appear to produce a regulatory factor that acts at the pre-B cell stage to induce the expression of Ig L chains and surface Ig. Bone marrow stromal cell conditioned medium was found to contain this factor and the active component was partially purified by HPLC. This stromal cell-derived factor had a m.w. between 16,000 and 20,000, was specifically neutralized by anti-IL-4 mAb, 11B11, and enhanced the proliferation of anti-mu-stimulated B cells. We also found that rIL-4 induced B cell formation in culture. In our studies, IL-1 had no direct effect on pre-B cell maturation, however, IL-1 was found to stimulate the production of IL-4 by both heterogeneous bone marrow stromal cells and a cloned stromal cell line, SCL-160. These effects of IL-1 on factor production by stromal cells were duplicated by the addition of bone marrow-derived macrophages to SCL-160 cells. We conclude that stromal cell-derived IL-4 is a physiologic stimulator for B cell generation. In addition, macrophages appear to play a role in B cell formation by regulating the production of IL-4 by stromal cells via the secretion of IL-1.
我们的实验研究了骨髓基质细胞对B淋巴细胞形成的调节作用。基质细胞似乎产生一种调节因子，该因子作用于前B细胞阶段，诱导Ig轻链和表面Ig的表达。发现骨髓基质细胞条件培养基含有这种因子，其活性成分通过高效液相色谱法进行了部分纯化。这种基质细胞衍生因子的分子量在16,000至20,000之间，可被抗IL-4单克隆抗体11B11特异性中和，并增强抗μ刺激的B细胞的增殖。我们还发现重组IL-4在培养中诱导B细胞形成。在我们的研究中，IL-1对前B细胞成熟没有直接影响，然而，发现IL-1可刺激异质性骨髓基质细胞和克隆的基质细胞系SCL-160产生IL-4。通过向SCL-160细胞中添加骨髓来源的巨噬细胞，可重现IL-1对基质细胞因子产生的这些作用。我们得出结论，基质细胞衍生的IL-4是B细胞生成的生理刺激物。此外，巨噬细胞似乎通过分泌IL-1调节基质细胞IL-4的产生，从而在B细胞形成中发挥作用。
