Greiner Axel, Tobollik Stephanie, Buettner Maike, Jungnickel Berit, Herrmann Kathrin, Kremmer Elisabeth, Niedobitek Gerald
Institute for Pathology, Friedrich-Alexander-University, 91054 Erlangen, Germany.
J Pathol. 2005 Apr;205(5):541-7. doi: 10.1002/path.1746.
Activation-induced cytidine deaminase (AID) is indispensable for class switch recombination and somatic hypermutation of immunoglobulin genes. Expression of AID has been detected in germinal centre centroblasts and in lymphomas derived from germinal centre cells. However, in situ studies of AID expression have until now been hampered by a lack of antibodies suitable for immunohistochemistry. To overcome this problem, an AID-specific monoclonal antibody suitable for immunohistochemical staining of formalin-fixed, paraffin wax-embedded tissue sections has been generated. This antibody was shown to detect AID expression in normal germinal centre B-cells as well as in non-Hodgkin lymphomas with a putative germinal centre origin. Using this antibody, a virtually exclusive cytoplasmic localization of AID in normal and neoplastic B-cells is shown. Employing a combination of immunohistochemistry and AID-specific in situ hybridization, it is demonstrated that AID is consistently expressed in the neoplastic cells of nodular lymphocyte-predominant Hodgkin lymphoma (HLnlp) but only infrequently in classical HL (cHL). This is in keeping with the notion that tumour cells of HLnlp represent transformed germinal centre B-cells showing evidence of somatic hypermutation. AID represents an additional marker useful in the differential diagnosis of HLnlp and cHL.
活化诱导胞苷脱氨酶(AID)对于免疫球蛋白基因的类别转换重组和体细胞超突变至关重要。已在生发中心母细胞以及源自生发中心细胞的淋巴瘤中检测到AID的表达。然而,迄今为止,由于缺乏适用于免疫组织化学的抗体,AID表达的原位研究受到了阻碍。为克服这一问题,现已制备出一种适用于福尔马林固定、石蜡包埋组织切片免疫组织化学染色的AID特异性单克隆抗体。该抗体可检测正常生发中心B细胞以及假定生发中心起源的非霍奇金淋巴瘤中的AID表达。使用该抗体显示,在正常和肿瘤性B细胞中,AID几乎仅定位于细胞质。采用免疫组织化学和AID特异性原位杂交相结合的方法,证明AID在结节性淋巴细胞为主型霍奇金淋巴瘤(HLnlp)的肿瘤细胞中持续表达,但在经典型HL(cHL)中仅偶尔表达。这与HLnlp的肿瘤细胞代表显示体细胞超突变证据的转化生发中心B细胞的观点一致。AID是HLnlp和cHL鉴别诊断中有用的额外标志物。