Poly(ADP-ribose) polymerase-1 (Parp-1)-deficient mice demonstrate abnormal antibody responses
Poly(ADP-ribose) polymerase-1 (Parp-1)-deficient mice demonstrate abnormal antibody responses
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DOI：
10.1111/j.1365-2567.2008.02921.x
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发表时间：
2009-06-01
期刊：
影响因子：
6.4
通讯作者：
Wagner, Simon D.
中科院分区：
文献类型：
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作者：
Ambrose, Helen E.;Willimott, Shaun;Wagner, Simon D.
受体蛋白的聚（ADP-核糖基化）是一种表观遗传修饰，涉及 DNA 链断裂修复、重组和转录。在这里，我们提供了聚（ADP-核糖）聚合酶-1（Parp-1）参与抗体反应的证据。 Parp-1(-/-) 小鼠的 T 细胞数量增加，总 B 细胞数量正常。边缘区B细胞数量轻度减少，滤泡B细胞数量得以保留。基础免疫球蛋白水平异常，免疫球蛋白G2a（IgG2a）水平降低，IgA和IgG2b水平升高。特异性抗体反应分析表明，T 细胞非依赖性反应正常，但 T 细胞依赖性反应明显减少。生发中心的大小和数量正常。体外纯化的 Parp-1(-/-) 小鼠 B 细胞增殖正常，IgM 分泌正常，向 IgG2a 的转换减少，但 IgA 分泌增加。总的来说，我们的结果表明 Parp-1 在正常 T 细胞依赖性抗体反应和同种型表达的调节中具有重要作用。我们推测 Parp-1 形成蛋白质复合物的一个组成部分，参与解决类别转换重组过程中发生的 DNA 双链断裂。
Poly(ADP-ribosylation) of acceptor proteins is an epigenetic modification involved in DNA strand break repair, recombination and transcription. Here we provide evidence for the involvement of poly(ADP-ribose) polymerase-1 (Parp-1) in antibody responses. Parp-1(-/-) mice had increased numbers of T cells and normal numbers of total B cells. Marginal zone B cells were mildly reduced in number, and numbers of follicular B cells were preserved. There were abnormal levels of basal immunoglobulins, with reduced levels of immunoglobulin G2a (IgG2a) and increased levels of IgA and IgG2b. Analysis of specific antibody responses showed that T cell-independent responses were normal but T cell-dependent responses were markedly reduced. Germinal centres were normal in size and number. In vitro purified B cells from Parp-1(-/-) mice proliferated normally and showed normal IgM secretion, decreased switching to IgG2a but increased IgA secretion. Collectively our results demonstrate that Parp-1 has essential roles in normal T cell-dependent antibody responses and the regulation of isotype expression. We speculate that Parp-1 forms a component of the protein complex involved in resolving the DNA double-strand breaks that occur during class switch recombination.