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  • 标题:Deletion of immunoglobulin β in developing B cells leads to cell death
  • 本地全文:下载
  • 作者:Eric Meffre ; Michel C. Nussenzweig
  • 期刊名称:Proceedings of the National Academy of Sciences
  • 印刷版ISSN:0027-8424
  • 电子版ISSN:1091-6490
  • 出版年度:2002
  • 卷号:99
  • 期号:17
  • 页码:11334-11339
  • DOI:10.1073/pnas.172369999
  • 语种:English
  • 出版社:The National Academy of Sciences of the United States of America
  • 摘要:Inducible gene-targeting experiments have shown that Ig{micro} expression is essential for maintaining survival of mature B cells, but the role of Ig{micro} 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 Ig{beta} cDNA as a transgene to complement Ig{beta}-/- mice. Transgenic Ig{beta} expression was found in proB and small preB cells and was extinguished in large preB and immature B cells. Ig{beta} 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 Ig{beta}. We conclude that Ig{beta} 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.
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