Luby T M, Sigurdardottir D, Berger E D, Selsing E
Immunology Program and Department of Pathology, Tufts University School of Medicine, Boston, MA 02111, USA.
Eur J Immunol. 2001 Oct;31(10):2866-75. doi: 10.1002/1521-4141(2001010)31:10<2866::aid-immu2866>3.0.co;2-0.
Analyses of H-chain transgenes have indicated that sequences situated between the mu intronic enhancer and the Cmu exons are important for mu gene expression. We have analyzed several variant mu transgenes and find that a sequence element located within or just upstream of Smu is important for mu transgene expression in both immature and mature B cells. This Smu -associated element appears to be required for functional mu expression in small, resting pre-B cells but not in proliferating pre-B cells. Our results also indicate that this element is responsible for previously reported differential transgene expression in resting and activated/proliferating mature B cells. However, our studies of knockout mice show that deletion of the Smu -associated element from the endogenous IgH locus does not alter early B cell maturation. This indicates that other elements within the H-chain locus can replace the function of the Smu -associated element at least to the mature B cell stage. Surprisingly, we also find that Smu deletion in the IgH locus does not affect levels of the sterile germ-line mu transcripts that are involved in B cell class switching, even though S-region sequences have been indicated to be important for the production of analogous germ-line transcripts for other isotypes.
重链转基因分析表明,位于μ内含子增强子和Cμ外显子之间的序列对μ基因表达很重要。我们分析了几个变异的μ转基因,发现位于Sμ内或其上游的一个序列元件对未成熟和成熟B细胞中的μ转基因表达很重要。这个与Sμ相关的元件似乎是小型静止前B细胞中功能性μ表达所必需的,但在增殖性前B细胞中则不是。我们的结果还表明,这个元件导致了先前报道的静止和活化/增殖成熟B细胞中转基因表达的差异。然而,我们对基因敲除小鼠的研究表明,从内源性IgH基因座中删除与Sμ相关的元件并不会改变早期B细胞成熟。这表明H链基因座中的其他元件至少在成熟B细胞阶段可以替代与Sμ相关的元件的功能。令人惊讶的是,我们还发现IgH基因座中的Sμ缺失并不影响参与B细胞类别转换的无菌种系μ转录本的水平,尽管S区序列已被表明对其他同种型的类似种系转录本的产生很重要。