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 mu rine lambda 5 (m lambda 5) gene and is transcriptionally active in pro-B an d pre-B lymphocytes. The lambda 5 and VpreB polypeptides together with the Ig mu H chain and the signal-transducing subunits, Iga and Ig beta, compris e 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 m ouse 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 gen e were detected in bone marrow pro-B and pre-B cells at the mRNA and protei n levels, suggesting that the 28-kb transgene fragment contains all the tra nscriptional elements necessary for the stage-specific B progenitor express ion of hu lambda 5. Flow cytometric and immunoprecipitation analyses of bon e marrow cells and Abelson murine leukemia virus-transformed pre-B cell lin es revealed the hu lambda 5 polypeptide on the cell surface and in associat ion with mouse Ig Cc 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 po lypeptide can biochemically and functionally substitute for m lambda 5 in v ivo in pre-E lymphocyte differentiation and proliferation, These studies on the mouse and human pre-B cell receptor provide a model system to investig ate some of the molecular requirements necessary for B cell development.