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

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

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ASJC Scopus subject areas

  • Immunology and Allergy
  • 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.