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Transgenic Human 5 Rescues the Murine 5 Nullizygous Phenotype¹

Mary E. Donohoe^2,*, Gabriele B. Beck-Engeser, Nils Lonberg, Hajime Karasuyama^§, Richard L. Riley^*, Hans-Martin Jäck^,¶ and Bonnie B. Blomberg^3,*

^* Department of Microbiology and Immunology, University of Miami School of Medicine, Miami, FL 33101; Department of Microbiology and Immunology, Loyola University, Stritch School of Medicine, Maywood, IL 60153; GenPharm International, San Jose, CA 95131; ^§ Department of Immunology, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan; and ^¶ Division of Molecular Immunology, Department of Internal Medicine IV, University of Erlangen, Erlangen, Germany

The human 5 (hu5) gene is the structural homologue of the murine 5 (m5) gene and is transcriptionally active in pro-B and pre-B lymphocytes. The 5 and VpreB polypeptides together with the Ig µ H chain and the signal-transducing subunits, Ig and Igß, comprise the pre-B cell receptor. To further investigate the pro-B/pre-B-specific transcription regulation of hu5 in an in vivo model, we generated mouse lines that contain a 28-kb genomic fragment encompassing the entire hu5 gene. High levels of expression of the transgenic hu5 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 hu5. Flow cytometric and immunoprecipitation analyses of bone marrow cells and Abelson murine leukemia virus-transformed pre-B cell lines revealed the hu5 polypeptide on the cell surface and in association with mouse Ig µ and mouse VpreB. Finally, we found that the hu5 transgene is able to rescue the pre-B lymphocyte block when bred onto the m5^-/- background. Therefore, we conclude that the hu5 polypeptide can biochemically and functionally substitute for m5 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.

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				R. Gisler and M. Sigvardsson The Human V-PreB Promoter Is a Target for Coordinated Activation by Early B Cell Factor and E47 J. Immunol., May 15, 2002; 168(10): 5130 - 5138. [Abstract] [Full Text] [PDF]