School of Biotechnology and Biomolecular Sciences, University of New South Wales, Kensington, NSW, Australia.
Am J Rhinol Allergy. 2010 Nov-Dec;24(6):416-21. doi: 10.2500/ajra.2010.24.3538.
It is generally assumed that all immunoglobulin isotopes develop under antigen selection pressure, leading to dramatic increases in antigen-binding affinity. As activated B cells proliferate, somatic mutations accumulate in the regions of the immunoglobulin gene associated with antigen binding. Emerging evidence from studies investigating mutations in variable region sequences of IgE antibodies suggest that IgE may develop under less selection pressure than other isotypes. Recent studies have focused on IgE mutation patterns in sequences from the blood of allergic individuals. There is, however, little evidence of these patterns in IgE sequences isolated from tissue.
Semi-nested reverse-transcription polymerase chain reaction was used to amplify the V region of IgE sequences from nasal tissue of individuals with chronic rhinosinusitis with nasal polyps (CRSwNPs). IgE sequences were analyzed for evidence of antigen selection and compared with previously reported IgE sequences from other inflammatory and allergic disorders and nonallergic individuals.
IgE sequences were successfully amplified from four individuals with CRSwNPs. Of 217 sequences amplified, 38 were unique, 31 of which were from tissue. Identification of the IGHV, IGHD, and IGHJ genes making up each sequence showed overrepresentation of an unusual gene in one individual, but otherwise normal gene usage. Mutation analysis revealed that only 5 of the 31 unique sequences from tissue show clear evidence of antigen selection.
With little influence from antigen selection, IgE antibodies are unlikely to be highly specific for antigens. Consequently, these findings have significant implications for the relevance of specific IgE, e.g., Staphylococcus aureus enterotoxin or fungal-specific IgE, in CRSwNP pathogenesis. Whether specific IgE expression is tightly related to pathogenesis or is merely a byproduct of B-cell interactions in local mucosa with colonizing organisms remains unresolved.
一般认为，所有免疫球蛋白同种型都是在抗原选择压力下产生的，从而导致抗原结合亲和力的显著提高。随着活化 B 细胞的增殖，免疫球蛋白基因中与抗原结合相关的区域会积累体细胞突变。来自研究 IgE 抗体可变区序列突变的新证据表明，IgE 的产生所受选择压力可能小于其他同种型。最近的研究集中在过敏性个体血液中 IgE 突变模式上。然而，在组织中分离的 IgE 序列中，这些模式的证据很少。
采用半巢式逆转录聚合酶链反应（PCR）扩增慢性鼻-鼻窦炎伴鼻息肉（CRSwNP）患者鼻组织中 IgE 序列的 V 区。对 IgE 序列进行抗原选择的证据进行分析，并与以前报道的其他炎症性和过敏性疾病以及非过敏性个体的 IgE 序列进行比较。
成功地从 4 例 CRSwNP 患者中扩增出 IgE 序列。在扩增的 217 个序列中，有 38 个是独特的，其中 31 个来自组织。组成每个序列的 IGHV、IGHD 和 IGHJ 基因的鉴定表明，一个个体中存在一种不寻常的基因过表达，但其他基因的使用是正常的。突变分析显示，只有 5 个来自组织的独特序列显示出明显的抗原选择证据。
由于抗原选择的影响很小，IgE 抗体不太可能对抗原具有高度特异性。因此，这些发现对特定 IgE（例如金黄色葡萄球菌肠毒素或真菌特异性 IgE）在 CRSwNP 发病机制中的相关性具有重要意义。特定 IgE 的表达是否与发病机制密切相关，还是仅仅是与定植生物在局部黏膜中 B 细胞相互作用的副产品，仍未解决。
