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

• Published in: Science immunology 2020-01, Vol.5 (43)
• Main Authors: Asrat, Seblewongel, Kaur, Navneet, Liu, Xia, Ben, Li-Hong, Kajimura, Daisuke, Murphy, Andrew J, Sleeman, Matthew A, Limnander, Andre, Orengo, Jamie M
• Format: Article
• Language: English
• ISSN: 2470-9468; 2470-9468
• DOI: 10.1126/sciimmunol.aav8402

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.