Expression of the AID protein in normal and neoplastic B cells
Expression of the AID protein in normal and neoplastic B cells
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DOI：
10.1182/blood-2004-04-1558
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发表时间：
2004-11-15
期刊：
影响因子：
20.3
通讯作者：
Polakiewicz, R
中科院分区：
文献类型：
--
作者：
Pasqualucci, L;Guglielmino, R;Polakiewicz, R
体细胞超突变（SHM）主要靶向生发中心（GC） B细胞中的免疫球蛋白可变区（IgV）基因，从而使抗体亲和成熟。约50%的弥漫性大b细胞淋巴瘤（DLBCLs）存在SHM功能异常，称为异常体细胞超突变（ASHM），可导致包括致癌基因在内的多个基因的5′序列发生突变。虽然SHM的机制在很大程度上是未知的，但它被证明需要激活诱导胞苷脱氨酶（AID）基因。AID mRNA在GC B细胞和GC源性淋巴瘤中表达，但AID蛋白的表达模式尚不清楚。使用2种特异性抗体，我们发现AID蛋白可以在胃癌成中心细胞及其转化的对应物（伯基特淋巴瘤）中检测到，但在胃癌前B细胞和胃癌后肿瘤（包括B细胞慢性淋巴细胞白血病和多发性骨髓瘤）中检测不到。dlbcl显示出不同水平的AID表达，这与IgV持续的高突变、ASHM或疾病亚型无关。最后，在正常和恶性B细胞中，AID蛋白主要定位于细胞质中。这些结果表明AID蛋白在正常和转化的GC B细胞中特异性表达；尽管如此，其主要的细胞质定位表明，其他机制可能调节其功能，并可能在淋巴瘤发生过程中发生改变。(C) 2004年由美国血液病学会出版。
Somatic hypermutation (SHM) targets primarily the immunoglobulin variable region (IgV) genes in germinal center (GC) B cells, thereby allowing antibody affinity maturation. A malfunction of SHM, termed aberrant somatic hypermutation (ASHM), was found in about 50% of diffuse large B-cell lymphomas (DLBCLs), leading to mutations in the 5' sequences of multiple genes, including oncogenes. Although the SHM mechanism is largely unknown, it was shown to require the activation-induced cytidine deaminase (AID) gene. AID mRNA is expressed in GC B cells and GC-derived lymphomas, but the pattern of expression of the AID protein is not known. Using 2 specific antibodies, here we show that the AID protein can be detected in GC centroblasts and their transformed counterpart (Burkitt lymphoma) but not in pre-GC B cells and post-GC neoplasms, including B-cell chronic lymphocytic leukemia and multiple myeloma. DLBCLs displayed variable levels of AID expression, which did not correlate with IgV ongoing hypermutation, ASHM, or disease subtype. Finally, both in normal and malignant B cells the AID protein appeared predominantly localized in the cytoplasm. These results indicate that the AID protein is specifically expressed in normal and transformed GC B cells; nonetheless, its predominantly cytoplasmic localization suggests that additional mechanisms may regulate its function and may be altered during lymphomagenesis. (C) 2004 by The American Society of Hematology.