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.