Department of Hematology, Leiden University Medical Center, Leiden, Netherlands.
School of Medicine, University of Magallanes, Punta Arenas, Chile.
Front Immunol. 2019 Jul 3;10:1543. doi: 10.3389/fimmu.2019.01543. eCollection 2019.
IgE-mediated allergic disease represents an increasing health problem. Although numerous studies have investigated IgE sequences in allergic patients, little information is available on the healthy IgE repertoire. IgM, IgG, IgA, and IgE transcripts from peripheral blood B cells of five healthy, non-atopic individuals were amplified by unbiased, template-switching, isotype-specific PCR. Complete VDJ regions were sequenced to near-exhaustion on the PacBio platform. Sequences were analyzed for clonal relationships, degree of somatic hypermutation, IGHV gene usage, evidence of antigenic selection, and N-linked glycosylation motifs. IgE repertoires appeared to be highly oligoclonal with preferential usage of certain IGHV genes compared to the other isotypes. IgE sequences carried more somatic mutations than IgM, yet fewer than IgG and IgA. Many IgE sequences contained N-linked glycosylation motifs. IgE sequences had no clonal relationship with the other isotypes. The IgE repertoire in healthy individuals is derived from relatively few clonal expansions without apparent relations to immune reactions that give rise to IgG or IgA. The mutational burden of normal IgE suggests an origin through direct class-switching from the IgM repertoire with little evidence of antigenic drive, and hence presumably low affinity for specific antigens. These findings are compatible with a primary function of the healthy IgE repertoire to occupy Fcε receptors for competitive protection against mast cell degranulation induced by allergen-specific, high-affinity IgE. This background knowledge may help to elucidate pathogenic mechanisms in allergic disease and to design improved desensitization strategies.
IgE 介导的过敏性疾病是一个日益严重的健康问题。尽管许多研究已经调查了过敏患者的 IgE 序列，但关于健康 IgE 库的信息却很少。通过无偏倚的、模板转换的、同种型特异性 PCR，扩增了来自五名健康、非过敏个体外周血 B 细胞的 IgM、IgG、IgA 和 IgE 转录本。在 PacBio 平台上对完整的 VDJ 区进行了近乎穷尽的测序。对序列进行了克隆关系、体细胞超突变程度、IGHV 基因使用、抗原选择证据和 N 连接糖基化模体的分析。IgE 库似乎高度寡克隆，与其他同种型相比，某些 IGHV 基因的使用更为优先。IgE 序列的体细胞突变比 IgM 多，但比 IgG 和 IgA 少。许多 IgE 序列含有 N 连接糖基化模体。IgE 序列与其他同种型没有克隆关系。健康个体的 IgE 库来自相对较少的克隆扩增，与产生 IgG 或 IgA 的免疫反应没有明显关系。正常 IgE 的突变负担表明其起源是通过直接从 IgM 库进行类别转换，几乎没有抗原驱动的证据，因此推测对特定抗原的亲和力较低。这些发现与健康 IgE 库的主要功能是占据 Fcε 受体，以竞争性保护过敏原特异性、高亲和力 IgE 诱导的肥大细胞脱颗粒一致。这些背景知识可能有助于阐明过敏疾病的发病机制，并设计改进的脱敏策略。
