Human lambda (λ)5 transgene does not rescue the murine λ5 nullizygous phenotype

The human (hu) λ5 gene is the orthologue of the murine (m) λ5 gene and is transcriptionally active in pro-B and pre-B lymphocytes. We generated huλ5 transgenic mouse lines to address the tissue- and stage-specific molecular transcription regulation and functional capabilities of huλ5. The huλ5 transgenic mice exhibit high levels of huλ5 mRNA expression, restricted to the pro-B and pre-B cell stages, indicating that the 28 kb XhoI transgene contains the necessary transcription elements for tissue- and stage-specific expression. When crossed with mλ5 nullizygous (-/-) mice, it was found that the huλ5 transgene does not rescue the mλ5 (-/-) phenotype of no or very low B lymphocyte numbers. Abelson-derived lines from huλ5 (+/-)/mλ5 (-/-) bone marrow show expression of a chimeric huλ5, mVpreB, m mu (μ) pre-B receptor (pre-BCR) and cell surface expression is indicated. Our results suggest that conformational and/or signaling differences exist between the mpre-BCR and this chimeric pre-BCR and that assembly and surface expression of the pre-BCR is not sufficient for B cell development.