First Author | Meffre E | Year | 2002 |
Journal | Proc Natl Acad Sci U S A | Volume | 99 |
Issue | 17 | Pages | 11334-9 |
PubMed ID | 12165571 | Mgi Jnum | J:78601 |
Mgi Id | MGI:2385520 | Doi | 10.1073/pnas.172369999 |
Citation | Meffre E, et al. (2002) Deletion of immunoglobulin beta in developing B cells leads to cell death. Proc Natl Acad Sci U S A 99(17):11334-9 |
abstractText | Inducible gene-targeting experiments have shown that Igmu expression is essential for maintaining survival of mature B cells, but the role of Igmu expression in immature B cell survival has not been determined. To assess whether continued B cell receptor (BCR) expression is required for bone marrow B cell precursor development and survival, we developed a method for conditional gene deletion in these cells. Recombination-activating gene regulatory elements were used to express Igbeta cDNA as a transgene to complement Igbeta(-/-) mice. Transgenic Igbeta expression was found in proB and small preB cells and was extinguished in large preB and immature B cells. Igbeta deletion from large preB cells and immature B cells resulted in cell death that could be rescued by transgenic bcl-2 expression. However, transgenic bcl-2 expression was unable to restore B cell development in the absence of Igbeta. We conclude that Igbeta expression is essential to maintain preB cell and immature B cell survival and to mediate B cell differentiation. In addition, complementation of null mutations with cDNAs under the control of heterologous bacterial artificial chromosomes is a useful method for cell-type-specific and developmentally regulated gene ablation in vivo. |