Chronic allergen exposure drives accumulation of long-lived IgE plasma cells in the bone marrow, giving rise to serological memory
Chronic allergen exposure drives accumulation of long-lived IgE plasma cells in the bone marrow, giving rise to serological memory
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DOI：
10.1126/sciimmunol.aav8402
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发表时间：
2020-01-01
影响因子：
24.8
通讯作者：
Orengo, Jamie M.
中科院分区：
文献类型：
--
作者：
Asrat, Seblewongel;Kaur, Navneet;Orengo, Jamie M.
免疫球蛋白E （IgE）在过敏性疾病中起重要作用。然而，IgE血清学记忆的来源仍然存在争议。我们利用双报告系统追踪小鼠的IgE（+）浆细胞，重新研究了过敏的血清学记忆机制。短期的过敏原暴露导致了IgE（+）浆细胞的产生，这些浆细胞主要存在于次级淋巴器官，产生的IgE不能使肥大细胞脱颗粒。相反，慢性过敏原暴露导致产生长寿的IgE（+）浆细胞，这些细胞主要来源于IgG1的顺序类转换，在骨髓中积累，并产生能够诱导过敏反应的IgE。在人类过敏者的骨髓中发现了IgE（+）浆细胞，而在非过敏者的骨髓中没有发现，这些细胞产生的过敏原特异性IgE在转移给小鼠时能够诱导肥大细胞脱颗粒。这些数据表明，长寿命的IgE（+）骨髓浆细胞在慢性过敏原暴露期间出现，并在小鼠和人类中建立血清学记忆。
Immunoglobulin E (IgE) plays an important role in allergic diseases. Nevertheless, the source of IgE serological memory remains controversial. We reexamined the mechanism of serological memory in allergy using a dual reporter system to track IgE(+) plasma cells in mice. Short-term allergen exposure resulted in the generation of IgE(+) plasma cells that resided mainly in secondary lymphoid organs and produced IgE that was unable to degranulate mast cells. In contrast, chronic allergen exposure led to the generation of long-lived IgE(+) plasma cells that were primarily derived from sequential class switching of IgG1, accumulated in the bone marrow, and produced IgE capable of inducing anaphylaxis. IgE(+) plasma cells were found in the bone marrow of human allergic, but not nonallergic donors, and allergen-specific IgE produced by these cells was able to induce mast cell degranulation when transferred to mice. These data demonstrate that long-lived IgE(+) bone marrow plasma cells arise during chronic allergen exposure and establish serological memory in both mice and humans.