Deutsches Rheuma-Forschungszentrum Berlin, Wissenschaftsgemeinschaft Leibniz, Berlin, Germany.
Allergol Int. 2010 Mar;59(1):1-8. doi: 10.2332/allergolint.10-RAI-0175.
As the key molecule of type-I-hypersensitivity, IgE provides specificity for the allergen and links it to the allergic effector functions. Antibodies are secreted by plasma cells and their precursors, the plasma blasts. The fate of plasma cells is a subject of controversy, with respect to their lifetime and persistence in the absence of allergen. In general, plasma cells were for a long time considered as short-lived end products of B-cell differentiation, and many of them are short-lived, although already for more than 20 years evidence has been provided that IgE-secreting plasma cells can persist over months. Today long-lived, "memory" plasma cells are considered to represent a distinct cellular entity of immunological memory, with considerable therapeutic relevance. Long-lived plasma cells resist current therapeutic and experimental approaches such as immunosuppression, e.g. cyclophosphamide, steroids, X-ray irradiation, anti-CD20 antibodies and anti-inflammatory drugs, while the chronic generation of short-lived plasma cells is sensitive to conventional immunosuppression. The seasonal variation in pollen-specific IgE can be suppressed by immunotherapy, indicating that component of the IgE response, which is stimulated with pollen allergen is susceptible to suppression. Targeting of the remaining long-lived, allergen-specific plasma cells, providing the stable IgE-titers, represents a therapeutic challenge. Here we discuss recent evidence suggesting, why current protocols for the treatment of IgE-mediated allergies fail: Memory plasma cells generated by inhalation of the allergen become long-lived and are maintained preferentially in the bone marrow. They do not proliferate, and are refractory to conventional therapies. Current concepts target plasma cells for depletion, e.g. the proteasome inhibitor bortezomib, BAFF and APRIL antagonists and autologous hematopoietic stem cell transplantation.
作为 I 型超敏反应的关键分子，IgE 为过敏原提供特异性，并将其与过敏效应功能联系起来。抗体由浆细胞及其前体细胞——浆母细胞分泌。浆细胞的命运是一个有争议的问题，涉及到它们在没有过敏原的情况下的寿命和持久性。一般来说，浆细胞长期以来被认为是 B 细胞分化的短命终产物，其中许多是短命的，尽管已经有 20 多年的证据表明 IgE 分泌浆细胞可以持续数月。如今，长寿命的“记忆”浆细胞被认为代表了免疫记忆的一个独特细胞实体，具有相当大的治疗相关性。长寿命浆细胞抵抗当前的治疗和实验方法，如免疫抑制，例如环磷酰胺、类固醇、X 射线照射、抗 CD20 抗体和抗炎药物，而短寿命浆细胞的慢性产生对常规免疫抑制敏感。花粉特异性 IgE 的季节性变化可以通过免疫疗法抑制，这表明与花粉过敏原刺激的 IgE 反应的一部分易受抑制。针对剩余的长寿命、过敏原特异性浆细胞，提供稳定的 IgE 滴度，代表了治疗挑战。在这里，我们讨论了最近的证据，表明为什么目前治疗 IgE 介导的过敏的方案失败：通过吸入过敏原产生的记忆浆细胞成为长寿命，并优先在骨髓中维持。它们不增殖，并且对常规治疗具有抗性。目前的概念针对浆细胞进行耗竭，例如蛋白酶体抑制剂硼替佐米、BAFF 和 APRIL 拮抗剂和自体造血干细胞移植。
