Homeostatic serum IgE is secreted by plasma cells in the thymus and enhances mast cell survival

Dong-il Kwon, Eun Seo Park, Mingyu Kim, Yoon Ha Choi, Myeong-seok Lee, Si-hyung Joo, Yeon-Woo Kang, Minji Lee, Saet-byeol Jo, Seung-Woo Lee, Jong Kyoung Kim () and You Jeong Lee ()
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Dong-il Kwon: Pohang University of Science and Technology (POSTECH)
Eun Seo Park: DGIST
Mingyu Kim: Pohang University of Science and Technology (POSTECH)
Yoon Ha Choi: Pohang University of Science and Technology (POSTECH)
Myeong-seok Lee: Seoul National University
Si-hyung Joo: Seoul National University
Yeon-Woo Kang: Pohang University of Science and Technology (POSTECH)
Minji Lee: Pohang University of Science and Technology (POSTECH)
Saet-byeol Jo: Pohang University of Science and Technology (POSTECH)
Seung-Woo Lee: Pohang University of Science and Technology (POSTECH)
Jong Kyoung Kim: Pohang University of Science and Technology (POSTECH)
You Jeong Lee: Pohang University of Science and Technology (POSTECH)

Nature Communications, 2022, vol. 13, issue 1, 1-13

Abstract: Abstract Increased serum levels of immunoglobulin E (IgE) is a risk factor for various diseases, including allergy and anaphylaxis. However, the source and ontogeny of B cells producing IgE under steady state conditions are not well defined. Here, we show plasma cells that develop in the thymus and potently secrete IgE and other immunoglobulins, including IgM, IgA, and IgG. The development of these IgE-secreting plasma cells are induced by IL-4 produced by invariant Natural Killer T cells, independent of CD1d-mediated interaction. Single-cell transcriptomics suggest the developmental landscape of thymic B cells, and the thymus supports development of transitional, mature, and memory B cells in addition to plasma cells. Furthermore, thymic plasma cells produce polyclonal antibodies without somatic hypermutation, indicating they develop via the extra-follicular pathway. Physiologically, thymic-derived IgEs increase the number of mast cells in the gut and skin, which correlates with the severity of anaphylaxis. Collectively, we define the ontogeny of thymic plasma cells and show that steady state thymus-derived IgEs regulate mast cell homeostasis, opening up new avenues for studying the genetic causes of allergic disorders.

Date: 2022
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DOI: 10.1038/s41467-022-29032-x

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