Research ArticleALLERGY

Chronic allergen exposure drives accumulation of long-lived IgE plasma cells in the bone marrow, giving rise to serological memory

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Science Immunology  10 Jan 2020:
Vol. 5, Issue 43, eaav8402
DOI: 10.1126/sciimmunol.aav8402

Locating the reservoir for IgE memory

Allergic diseases persist when the immune system chronically churns out allergen-specific IgE antibodies. Identifying the tissue location of IgE+ memory plasma cells is complicated by their very low frequency. Asrat et al. tracked IgE+ memory plasma cell development after intranasal exposure of mice to house dust mite allergen using fluorescent reporter transgenes to mark IgE+ plasma cells. In mice repeatedly exposed to allergen for 15 weeks, long-lived IgE+ memory plasma cells emerged in the bone marrow. IgE+ memory plasma cells in the bone marrow of both mice and allergic human patients yielded pathogenic IgE antibodies capable of eliciting anaphylaxis after transfer. Identification of long-lived plasma cells as the chief source of IgE memory may assist in developing new therapeutic approaches for chronic allergic diseases.

Abstract

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.

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