Transgenic human λ5 rescues the murine λ5 nullizygous phenotype

Mary E. Donohoe, Gabriele B. Beck-Engeser, Nils Lonberg, Hajime Karasuyama, Richard L Riley, Hans Martin Jäck, Bonnie B Blomberg

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

The human λ5 (huλ5) gene is the structural homologue of the murine λ5 (mλ5) gene and is transcriptionally active in pro-B and pre-B lymphocytes. The λ5 and VpreB polypeptides together with the Ig μ H chain and the signal-transducing subunits, Igα and Igβ, comprise the pre-B cell receptor. To further investigate the pro-B/pre-B-specific transcription regulation of huλ5 in an in vivo model, we generated mouse lines that contain a 28-kb genomic fragment encompassing the entire huλ5 gene. High levels of expression of the transgenic huλ5 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 huλ5. Flow cytometric and immunoprecipitation analyses of bone marrow cells and Abelson murine leukemia virus-transformed pre-B cell lines revealed the huλ5 polypeptide on the cell surface and in association with mouse Ig μ and mouse VpreB. Finally, we found that the huλ5 transgene is able to rescue the pre-B lymphocyte block when bred onto the mλ5(-/-) background. Therefore, we conclude that the huλ5 polypeptide can biochemically and functionally substitute for mλ5 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.

Original languageEnglish
Pages (from-to)5269-5276
Number of pages8
JournalJournal of Immunology
Volume164
Issue number10
StatePublished - May 15 2000

Fingerprint

B-Lymphoid Precursor Cells
Phenotype
Pre-B Cell Receptors
Transgenes
Peptides
Genes
Abelson murine leukemia virus
Immunoglobulin Subunits
Immunoprecipitation
Bone Marrow Cells
B-Lymphocytes
Bone Marrow
Cell Line
Messenger RNA
Proteins

ASJC Scopus subject areas

  • Immunology

Cite this

Donohoe, M. E., Beck-Engeser, G. B., Lonberg, N., Karasuyama, H., Riley, R. L., Jäck, H. M., & Blomberg, B. B. (2000). Transgenic human λ5 rescues the murine λ5 nullizygous phenotype. Journal of Immunology, 164(10), 5269-5276.

Transgenic human λ5 rescues the murine λ5 nullizygous phenotype. / Donohoe, Mary E.; Beck-Engeser, Gabriele B.; Lonberg, Nils; Karasuyama, Hajime; Riley, Richard L; Jäck, Hans Martin; Blomberg, Bonnie B.

In: Journal of Immunology, Vol. 164, No. 10, 15.05.2000, p. 5269-5276.

Research output: Contribution to journalArticle

Donohoe, ME, Beck-Engeser, GB, Lonberg, N, Karasuyama, H, Riley, RL, Jäck, HM & Blomberg, BB 2000, 'Transgenic human λ5 rescues the murine λ5 nullizygous phenotype', Journal of Immunology, vol. 164, no. 10, pp. 5269-5276.
Donohoe ME, Beck-Engeser GB, Lonberg N, Karasuyama H, Riley RL, Jäck HM et al. Transgenic human λ5 rescues the murine λ5 nullizygous phenotype. Journal of Immunology. 2000 May 15;164(10):5269-5276.
Donohoe, Mary E. ; Beck-Engeser, Gabriele B. ; Lonberg, Nils ; Karasuyama, Hajime ; Riley, Richard L ; Jäck, Hans Martin ; Blomberg, Bonnie B. / Transgenic human λ5 rescues the murine λ5 nullizygous phenotype. In: Journal of Immunology. 2000 ; Vol. 164, No. 10. pp. 5269-5276.
@article{4ae33ef78876495d9bfefdb26789095d,
title = "Transgenic human λ5 rescues the murine λ5 nullizygous phenotype",
abstract = "The human λ5 (huλ5) gene is the structural homologue of the murine λ5 (mλ5) gene and is transcriptionally active in pro-B and pre-B lymphocytes. The λ5 and VpreB polypeptides together with the Ig μ H chain and the signal-transducing subunits, Igα and Igβ, comprise the pre-B cell receptor. To further investigate the pro-B/pre-B-specific transcription regulation of huλ5 in an in vivo model, we generated mouse lines that contain a 28-kb genomic fragment encompassing the entire huλ5 gene. High levels of expression of the transgenic huλ5 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 huλ5. Flow cytometric and immunoprecipitation analyses of bone marrow cells and Abelson murine leukemia virus-transformed pre-B cell lines revealed the huλ5 polypeptide on the cell surface and in association with mouse Ig μ and mouse VpreB. Finally, we found that the huλ5 transgene is able to rescue the pre-B lymphocyte block when bred onto the mλ5(-/-) background. Therefore, we conclude that the huλ5 polypeptide can biochemically and functionally substitute for mλ5 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.",
author = "Donohoe, {Mary E.} and Beck-Engeser, {Gabriele B.} and Nils Lonberg and Hajime Karasuyama and Riley, {Richard L} and J{\"a}ck, {Hans Martin} and Blomberg, {Bonnie B}",
year = "2000",
month = "5",
day = "15",
language = "English",
volume = "164",
pages = "5269--5276",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "10",

}

TY - JOUR

T1 - Transgenic human λ5 rescues the murine λ5 nullizygous phenotype

AU - Donohoe, Mary E.

AU - Beck-Engeser, Gabriele B.

AU - Lonberg, Nils

AU - Karasuyama, Hajime

AU - Riley, Richard L

AU - Jäck, Hans Martin

AU - Blomberg, Bonnie B

PY - 2000/5/15

Y1 - 2000/5/15

N2 - The human λ5 (huλ5) gene is the structural homologue of the murine λ5 (mλ5) gene and is transcriptionally active in pro-B and pre-B lymphocytes. The λ5 and VpreB polypeptides together with the Ig μ H chain and the signal-transducing subunits, Igα and Igβ, comprise the pre-B cell receptor. To further investigate the pro-B/pre-B-specific transcription regulation of huλ5 in an in vivo model, we generated mouse lines that contain a 28-kb genomic fragment encompassing the entire huλ5 gene. High levels of expression of the transgenic huλ5 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 huλ5. Flow cytometric and immunoprecipitation analyses of bone marrow cells and Abelson murine leukemia virus-transformed pre-B cell lines revealed the huλ5 polypeptide on the cell surface and in association with mouse Ig μ and mouse VpreB. Finally, we found that the huλ5 transgene is able to rescue the pre-B lymphocyte block when bred onto the mλ5(-/-) background. Therefore, we conclude that the huλ5 polypeptide can biochemically and functionally substitute for mλ5 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.

AB - The human λ5 (huλ5) gene is the structural homologue of the murine λ5 (mλ5) gene and is transcriptionally active in pro-B and pre-B lymphocytes. The λ5 and VpreB polypeptides together with the Ig μ H chain and the signal-transducing subunits, Igα and Igβ, comprise the pre-B cell receptor. To further investigate the pro-B/pre-B-specific transcription regulation of huλ5 in an in vivo model, we generated mouse lines that contain a 28-kb genomic fragment encompassing the entire huλ5 gene. High levels of expression of the transgenic huλ5 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 huλ5. Flow cytometric and immunoprecipitation analyses of bone marrow cells and Abelson murine leukemia virus-transformed pre-B cell lines revealed the huλ5 polypeptide on the cell surface and in association with mouse Ig μ and mouse VpreB. Finally, we found that the huλ5 transgene is able to rescue the pre-B lymphocyte block when bred onto the mλ5(-/-) background. Therefore, we conclude that the huλ5 polypeptide can biochemically and functionally substitute for mλ5 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.

UR - http://www.scopus.com/inward/record.url?scp=0034658071&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034658071&partnerID=8YFLogxK

M3 - Article

C2 - 10799888

AN - SCOPUS:0034658071

VL - 164

SP - 5269

EP - 5276

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 10

ER -