Regulation of B cell differentiation in bone marrow

1998 Fiscal Year Final Research Report Summary

• Project/Area Number: 09836003
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: 免疫の制御機構
• Research Institution: Tokyo Institute of Technology
• Principal Investigator: KUDO Akira Tokyo Institute of Technology, Faculty of Bioscience and Biotechnology, Professor (70178002)
• Co-Investigator(Kenkyū-buntansha): TAKESHITA Sunao Tokyo Institute of Technology, Faculty of Bioscience and Biotechnology, Assistant Professor (50263009)
• Project Period (FY): 1997 – 1998
• Keywords: lg rearrangement / λ5 / VpreB / surrogate L chain / preB cell receptor / B cell differentiation

Research Abstract

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.