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

Elevated levels of IgE is associated with a range of allergic pathology but the source of such IgE producing B cells during the steady state is poorly understood. Here, Kwon et al. show that homeostatic IgE is secreted by plasma cells in the thymus and link this to mast cell survival. 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.

Automated summary

This study demonstrates that plasma cells in the thymus secrete IgE and other immunoglobulins, and their development is induced by IL-4 and related to mast cell survival. Thymic B cells go through transitional, mature, memory, and plasma cell stages. Thymic plasma cells produce polyclonal antibodies without somatic hypermutation and regulate mast cell homeostasis in the gut and skin, which is linked to the severity of anaphylaxis.