Transgenic human lambda 5 rescues the murine lambda 5 nullizygous phenotype.
The human lambda 5 (hu lambda 5) gene is the structural homologue of the murine lambda 5 (m lambda 5) gene and is transcriptionally active in pro-B and pre-B lymphocytes. The lambda 5 and VpreB polypeptides together with the Ig mu H chain and the signal-transducing subunits, Ig alpha and Ig beta, comprise the pre-B cell receptor. To further investigate the pro-B/pre-B-specific transcription regulation of hu lambda 5 in an in vivo model, we generated mouse lines that contain a 28-kb genomic fragment encompassing the entire hu lambda 5 gene. High levels of expression of the transgenic hu lambda 5 gene were detected in bone marrow pro-B and pre-B cells at the mRNA and protein levels, suggesting that the 28-kb transgene fragment contains all the transcriptional elements necessary for the stage-specific B progenitor expression of hu lambda 5. Flow cytometric and immunoprecipitation analyses of bone marrow cells and Abelson murine leukemia virus-transformed pre-B cell lines revealed the hu lambda 5 polypeptide on the cell surface and in association with mouse Ig mu and mouse VpreB. Finally, we found that the hu lambda 5 transgene is able to rescue the pre-B lymphocyte block when bred onto the m lambda 5-/- background. Therefore, we conclude that the hu lambda 5 polypeptide can biochemically and functionally substitute for m lambda 5 in vivo in pre-B lymphocyte differentiation and proliferation. These studies on the mouse and human pre-B cell receptor provide a model system to investigate some of the molecular requirements necessary for B cell development.
Donohoe
M E
ME
Department of Microbiology, University of Miami School of Medicine, Miami, FL 33101, USA.
Beck-Engeser
G B
GB
Lonberg
N
N
Karasuyama
H
H
Riley
R L
RL
Jäck
H M
HM
Blomberg
B B
BB
D000011:Abelson murine leukemia virus / Q000235:genetics; D000818:Animals; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D001666:Binding Sites, Antibody / Q000235:genetics; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D019070:Cell Lineage / Q000235:genetics / Q000276:immunology; D003433:Crosses, Genetic; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000378:metabolism; D007147:Immunoglobulin Light Chains; D054444:Immunoglobulin Light Chains, Surrogate; D007146:Immunoglobulin lambda-Chains / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D007148:Immunoglobulin mu-Chains / Q000378:metabolism; D016130:Immunophenotyping; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D011947:Receptors, Antigen, B-Cell / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D013737:Testis / Q000276:immunology / Q000378:metabolism; D013950:Thymus Gland / Q000276:immunology / Q000378:metabolism; D019076:Transgenes / Q000276:immunology*
D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D054444:Immunoglobulin Light Chains, Surrogate; D007146:Immunoglobulin lambda-Chains; D007148:Immunoglobulin mu-Chains; D008562:Membrane Glycoproteins; D011947:Receptors, Antigen, B-Cell