Miyazaki T, Kato I, Takeshita S, Karasuyama H, Kudo A
Department of Life Science, Tokyo Institute of Technology, 4259 Nagatsuta, Midori-ku, Yokohama 226-8501, Japan.
Int Immunol. 1999 Aug;11(8):1195-202. doi: 10.1093/intimm/11.8.1195.
Lambda5 associates with V(pre-B) to form the surrogate light (L) chain. The phenotype of lambda5 knockout mice showed severe impairment of B cell development from pro-B to immature B cell stages. To investigate the function of the surrogate L chain at this stage, we restored expression of lambda5 to lambda5-deficient pro-B cell lines which were established from bone marrow cells of lambda5 knockout mice in the presence of IL-7 and a stromal cell line. Some of these lines are severely impaired in B cell development from pro-B to immature B cell stages as is seen in vivo in lambda5 knockout mice. Restoration of lambda5 protein by retroviral-mediated gene transfer into established lambda5-deficient pro-B cell lines induced rearrangement of the Ig kappa L chain genes after removal of IL-7 from the culture. Immunoprecipitation revealed that the restored lambda5 in the cell line is coupled with V(pre-B) to form the surrogate L chain. The results demonstrate that formation of a complete surrogate L chain, consisting of both lambda5 and V(pre-B), stimulates efficient rearrangement of the kappa L chain genes.
λ5与前B细胞受体(V(pre-B))结合形成替代轻链(L链)。λ5基因敲除小鼠的表型显示,从前B细胞到未成熟B细胞阶段,B细胞发育严重受损。为了研究此阶段替代L链的功能,我们将λ5的表达恢复到λ5缺陷的前B细胞系中,这些细胞系是在白细胞介素-7(IL-7)和一种基质细胞系存在的情况下,从λ5基因敲除小鼠的骨髓细胞建立的。其中一些细胞系在从前B细胞到未成熟B细胞阶段的B细胞发育中严重受损,这与λ5基因敲除小鼠体内的情况相同。通过逆转录病毒介导的基因转移,将λ5蛋白恢复到已建立的λ5缺陷前B细胞系中,在从培养物中去除IL-7后,诱导了免疫球蛋白κ轻链(Ig κ L链)基因的重排。免疫沉淀显示,细胞系中恢复的λ5与V(pre-B)结合形成替代L链。结果表明,由λ5和V(pre-B)组成的完整替代L链的形成,刺激了κ L链基因的有效重排。