Regulation of B cell differentiation in bone marrow

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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.