Lambda5 is required for rearrangement of the Ig kappa light chain gene in pro-B cell lines.
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.
Department of Life Science, Tokyo Institute of Technology, 4259 Nagatsuta, Midori-ku, Yokohama 226-8501, Japan.
T
T
Miyazaki
I
I
Kato
S
S
Takeshita
H
H
Karasuyama
A
A
Kudo
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D001854:Bone Marrow Cells; D002454:Cell Differentiation; D002460:Cell Line; D005786:Gene Expression Regulation; D015328:Gene Rearrangement, B-Lymphocyte, Light Chain; D018014:Gene Transfer Techniques; D005803:Genes, Immunoglobulin; D005822:Genetic Vectors; D007147:Immunoglobulin Light Chains; D054444:Immunoglobulin Light Chains, Surrogate; D007135:Immunoglobulin Variable Region / Q000235:genetics / Q000378:metabolism; D007145:Immunoglobulin kappa-Chains / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D007146:Immunoglobulin lambda-Chains / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D015851:Interleukin-7 / Q000276:immunology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D011233:Precipitin Tests; D012190:Retroviridae / Q000235:genetics
D007147:Immunoglobulin Light Chains; D054444:Immunoglobulin Light Chains, Surrogate; D007135:Immunoglobulin Variable Region; D007145:Immunoglobulin kappa-Chains; D007146:Immunoglobulin lambda-Chains; D015851:Interleukin-7; D008562:Membrane Glycoproteins