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.

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Aberrant activation of Ras has been implicated in aggressiveness of breast cancer. Among Ras isoforms (H-, K-, and N-), H-Ras has been known to be primarily responsible for invasion and metastasis of breast cancer cells. Phosphorylation of serine (Ser) or threonine (Thr) is a key regulatory mechanism responsible for controlling activities and functions of various proteins involved in intracellular signal transduction. Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1, Pin1 changes the conformation of a subset of proteins phosphorylated on Ser/Thr that precedes proline (Pro). In this study we have found that Pin1 is highly overexpressed in human breast tumor tissues and H-Ras transformed human mammary epithelial (H-Ras MCF10A) and MDA-MB-231 breast cancer cells. Notably, Pin1 directly bound to the activated form of H-Ras harbouring a Ser/Thr-Pro motif. Pharmacologic inhibition of Pin1 reduced clonogenicity of MDA-MB-231 human breast cancer cells. Paclitaxel accelerates apoptosis in Pin1 silenced H-Ras MCF10A cells. MDR genes (MDR1 and MRP4) were significantly downregulated in MDA-MB-231 cells stably silenced for Pin1. We speculate that Pin1 interacts with GTP-H-Ras, thereby upregulating the expression of drug resistance genes, which confers survival advantage and aggressiveness of breast cancer cells under chemotherapy.