Regulation of B cell differentiation in bone marrow

λ5与VpreB结合形成替代轻链。λ5基因敲除小鼠的表型显示B细胞从前B细胞到未成熟B细胞阶段的发育严重受损。为了研究替代轻链在这一阶段的功能，我们恢复了λ5至λ 5缺陷型preB细胞系的表达。这些细胞系中的一些在B细胞从前B到未成熟B细胞阶段的发育中严重受损，如在λ5敲除小鼠体内所见。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缺陷型preB细胞系中，诱导免疫球蛋白κ轻链基因重排。免疫沉淀显示细胞系中恢复的λ5与VpreB偶联形成替代轻链。结果表明，由λ5和VpreB组成的完整替代轻链的形成可以与μ重链结合形成preB细胞受体复合物，并且该复合物刺激k轻链基因的有效重排。

λ5 associates with VpreB to form the surrogate light chain. The phenotype of λ5 knock out mice showed severe impairment of B cell development from preB to immature B cell stages. To investigate the function of the surrogate light chain at this stage, we restored expression of λ5 to λ5 deficient preB cell lines.λ5 deficient preB cell lines from bone marrow of λ5 knock out mice were established in the presence of IL-7 and a stromal cell line. Some of these lines are, severely impaired in B cell development from preB to immature B cell stages as is seen in-vivo in λ5 knockout mice. Restoration of λ5 protein by retroviral-mediated gene transfer into established λ5 deficient preB cell lines induced the rearrangement of the immunoglobulin κ light chain genes. Immunoprecipitation revealed that the restored λ5 in the cell line is coupled with VpreB to form the surrogate light chain. The results suggest that formation of a complete surrogate light chain, consisting of both λ5 and VpreB, can associate with μ heavy chain in forming a preB cell receptor complex and that this complex stimulates efficient rearrangement of k light chain genes.