Narendran A, Cumano A, Dorshkind K, Paige C J
Division of Cellular and Molecular Biology, Ontario Cancer Institute, Toronto, Canada.
Eur J Immunol. 1992 Apr;22(4):1001-6. doi: 10.1002/eji.1830220419.
The expression of an X-linked defect in the CBA/N strain of mice has been found to result in a number of immune abnormalities. These include low responsiveness to antigens and a greatly reduced ability to respond to many of the common B cell mitogens. An in vitro manifestation of this condition is the virtual inability of CBA/N B cells to form colonies in lipopolysaccharide (LPS)-containing semisolid agar cultures. In this report we show evidence that the colony-forming ability of CBA/N spleen cells can be effectively restored by the bone marrow stromal-derived cell line S17. Spleen cells from 4-5-week-old homozygous CBA/N female mice were grown in double-layer agar cultures containing S17 feeder layers. Control cultures contained the fibroblast-like cell line 95.17 or were treated with medium alone. It was found that at an input cell concentration of 10(4) cells per plate, CBA/N colony formation was increased from a frequency of approximately 1 in 5,000 to 1 in 50 total splenic cells. Studies with purified surface immunoglobulin-positive cells indicate the direct involvement of S17 in this process. The CBA/N colonies formed were dependent on the presence of a mitogen (LPS) and secreted detectable amounts of IgM. Major implications of these findings and the application of this assay system to study the CBA/N defect have been discussed.
已发现,CBA/N品系小鼠中X连锁缺陷的表达会导致多种免疫异常。这些异常包括对抗原的低反应性以及对许多常见B细胞有丝分裂原的反应能力大幅降低。这种情况在体外的表现是,CBA/N B细胞几乎无法在含脂多糖(LPS)的半固体琼脂培养物中形成集落。在本报告中,我们展示了证据,表明骨髓基质衍生的细胞系S17可有效恢复CBA/N脾细胞的集落形成能力。将4 - 5周龄纯合CBA/N雌性小鼠的脾细胞在含有S17饲养层的双层琼脂培养物中培养。对照培养物含有成纤维细胞样细胞系95.17或仅用培养基处理。结果发现,在每平板输入细胞浓度为10(4)个细胞时,CBA/N集落形成频率从约每5000个脾细胞中有1个增加到每50个脾细胞中有1个。对纯化的表面免疫球蛋白阳性细胞的研究表明S17直接参与了这一过程。形成的CBA/N集落依赖于有丝分裂原(LPS)的存在,并分泌可检测量的IgM。已讨论了这些发现的主要意义以及该检测系统在研究CBA/N缺陷中的应用。