Department of Microbiology and Immunology, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA.
Genes Dev. 2013 Jan 1;27(1):1-17. doi: 10.1101/gad.200014.112.
The mechanisms by which B cells somatically engineer their genomes to generate the vast diversity of antibodies required to challenge the nearly infinite number of antigens that immune systems encounter are of tremendous clinical and academic interest. The DNA cytidine deaminase activation-induced deaminase (AID) catalyzes two of these mechanisms: class switch recombination (CSR) and somatic hypermutation (SHM). Recent discoveries indicate a significant promiscuous targeting of this B-cell mutator enzyme genome-wide. Here we discuss the various regulatory elements that control AID activity and prevent AID from inducing genomic instability and thereby initiating oncogenesis.
B 细胞通过体细胞工程其基因组产生大量的抗体以应对免疫系统遇到的几乎无限数量的抗原,其机制具有巨大的临床和学术意义。DNA 胞嘧啶脱氨酶激活诱导脱氨酶(AID)催化其中两种机制:类别转换重组(CSR)和体细胞高频突变(SHM)。最近的发现表明,这种 B 细胞诱变酶在全基因组范围内存在显著的广泛靶向性。在这里,我们讨论了控制 AID 活性的各种调节元件,这些元件可防止 AID 引起基因组不稳定性,从而启动肿瘤发生。