Type 2-polarized memory B cells hold allergen-specific IgE memory
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE248256 | GEO | 2023/11/25
REPOSITORIES: GEO
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Project description:Summary: Long-lived IgE plasma cells reside in the bone marrow of allergic mice and atopic humans, confer IgE serological memory and produce allergen-specific IgE that can drive anaphylaxis. Abstract: Immunoglobulin E (IgE) plays an important role in allergic diseases. Nevertheless, the source of IgE serological memory remains controversial. We re-examined the mechanism of serological memory in allergy using a dual-reporter system to track IgE plasma cells (PCs) in mice. Short-term allergen exposure resulted in the generation of IgE plasma cells that resided mainly in secondarylymphoid 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 (BM) and produced IgE capable of inducing anaphylaxis. Most importantly, IgE plasma cells were found in the BM of human allergic, but not non-allergic donors, and allergen-specific IgE produced by these cells was able to induce mast cell degranulation when transferred to mice. These data demonstrate that longlived IgE BMPCs arise during chronic allergen exposure and establish serological memory in both mice and humans.
2019-11-16 | GSE140435 | GEO
Project description:IgE antibody is known as a common mediator of allergic responses, generally produced in type 2 immune responses to allergens. It is known that IgE binding to FcεRI without allergen binding promotes survival or proliferation of mast cells, basophils and other cells. Thus, spontaneously produced IgE, namely natural IgE, can increase an individual’s susceptibility to allergic diseases. Mice with a genetic defect in MyD88, a major signaling molecule downstream of Toll-like receptors, have a high level of serum natural IgE, the mechanism for which remains unknown. Here, we demonstrated that the maintenance of high serum IgE levels depends on memory B cells (MBCs). IgE from plasma cells and the sera from most of Myd88–/– mice, but none of Myd88+/– mice, recognized Streptococcus azizii (S. azizii), a commensal bacterium over-represented in the lung of Myd88–/– mice. IgG1+ MBCs from spleen also recognized S. azizii. The serum IgE levels declined by administration of antibiotics and were boosted by challenge with S. azizii in Myd88–/– mice. Moreover, bulk IgH repertoire analysis revealed that CDR3 sequences were highly shared between IgE+ PCs and IgG1+ or IgG2+ MBCs, indicating the contribution of S. azizii-specific IgG1+ MBCs to the natural IgE production.
2023-01-27 | GSE220657 | GEO
Project description:IgE-binding monocytes are a rare peripheral immune cell type involved in the allergic response through binding of IgE on their surface. IgE-binding monocytes are present in both healthy and allergic individuals. We performed RNA sequencing to ask how the function of IgE-binding monocytes differs in the context of allergy. Using a large animal model of allergy, equine Culicoides hypersensitivity, we compared the transcriptome of IgE-binding monocytes in allergic and non-allergic horses at two seasonal timepoints: (i) when allergic animals were clinical healthy, in the winter “Remission Phase”, and (ii) during chronic disease, in the summer “Clinical Phase”. Most transcriptional differences between allergic and non-allergic horses occurred only during the “Remission Phase”, suggesting principal differences in monocyte function even in the absence of allergen exposure. F13A1, a subunit of fibrinoligase, was significantly upregulated at both timepoints in allergic horses. This suggested a role for increased fibrin deposition in the coagulation cascade to promote allergic inflammation. IgE-binding monocytes also downregulated CCR10 expression in allergic horses during the “Clinical Phase”, suggesting a defect in maintenance of skin homeostasis, which further promotes allergic inflammation. Together, this transcriptional analysis provides valuable clues into the mechanisms used by IgE-binding monocytes in allergic individuals.
2023-05-15 | GSE231427 | GEO
Project description:Food allergy is caused by allergen-specific IgE but little is known about the B cell memory of persistent responses. Here we describe in pediatric peanut allergy a population of CD23+IgG1 memory B cells that contains peanut-specific clones and generates IgE plasma cells on activation. Through single cell transcriptomics and B cell receptor (BCR) sequencing, we characterized FCER2/CD23+ IgG1 memory B cells co-expressing IL4R, IL13RA1, IGHE and carrying highly mutated BCRs. Further we found that peanut allergen (Ara h 2)-specific B cells were mostly IgG1 memory cells, carried highly mutated BCRs compared to diphtheria toxin-specific B cells, and expressed FCER2 and germlin IGHE. Our findings suggest that CD23+IgG1+ memory B cells transcribing IGHE are a unique memory population containing precursors for pathogenic IgE in food allergy.
2023-11-16 | GSE208235 | GEO
Project description:Allergy is one of the most prevalent chronic diseases, affecting hundreds of millions of people worldwide. In allergy, environmental allergens induce B cells to undergo class switch recombination and produce Immunoglobulin E (IgE) antibodies. IgE is a key molecule that mediates allergic responses by coating mast cell or basophil surfaces and inducing degranulation upon binding a specific allergen. IgE can also be spontaneously produced in the absence of exogenous allergens, yet the origin, regulation, and functions of such “natural” IgE still remains largely unknown. Here, we discovered that glucocorticoids, which are steroid stress hormones, enhance IgE isotype class switching in B cells both in vivo and ex vivo without antigenic challenge. Such IgE class switching is promoted by B cell-intrinsic glucocorticoid receptor signaling that reinforces CD40 signaling and synergizes with the IL-4/STAT6 pathway. In addition, we found that rare B cells in the mesenteric lymph nodes are responsible for the production of glucocorticoid-inducible IgE. Furthermore, we showed that locally produced glucocorticoids in the gut may induce natural IgE during perturbations of gut homeostasis such as dysbiosis. Notably, mice preemptively treated with glucocorticoids were protected from subsequent IgE-mediated pathogenic anaphylaxis in vivo. Together, our results suggest that glucocorticoids, classically considered to be broadly immunosuppressive, have a selective immunostimulatory role in B cells.
2022-09-09 | GSE203542 | GEO
Project description:Allergen exposure was thought to play a critical role in the etiology of AR. And allergen avoidance, the practice of avoiding exposure to allergens, has been generally advised as the management of AR. However, the effect is uncertain and the underlying mechanism is far from known. We used gene expression microarrays to identify genes differentially regulated by allergen avoidance in allergic rhinitis mouse model.
2013-11-28 | GSE52804 | GEO
Project description:Best known for their roles in allergic diseases, the physiologic function of immunoglobulin E (IgE) and mast cells (the so-called allergy module of immunity) has been enigmatic. Recent evidence shows that allergic reactions can help to protect against the toxicity of venoms. As bacteria are a potent alternative source of toxins, we assessed the potential role of the allergy module in antibacterial host defense. We observed that the immune response against S. aureus skin infection includes specific IgEs and substantially improves systemic host defense against secondary S. aureus infections in mice. This acquired protection depends on functional IgE effector mechanisms and mast cells. Our results reveal the powerful antibacterial potential of the allergy module and therefore a novel physiologic function of IgEs and mast cells.
2020-09-10 | PXD019107 | Pride
Project description:IgE-producing memory cells are hard to detect in the periphery. Here, we sorted IgE+ memory B cells from allergic patients who had received allergen-immunotherapy for grass pollen. Cells were FACS-sorted and subseuqenlty sequenced by single cell RNAseq to determine isotype and phenotype. Two out of 90 cells were determiend to be true IgE producing memory B cells.
2019-07-31 | GSE117803 | GEO
Project description:Gene expression (Npatients = 21, Ncontrols = 21) of CD4+ T-cells failed to seperate patients with seasonal allergic rhinitis (SAR) and healthy controls in an in vitro model system in which purified PBMCs from patients and healthy controls were challenged with allergen for 7 days.
2013-08-28 | GSE50223 | GEO
Project description:Seasonal allergic rhinitis (SAR) is a complex disease that is caused by many interacting genes and environmental factors. It is also an excellent model disease for clinical studies; it is common, it is seasonal, and since it takes place in the nasal cavity it can be studied in vivo non-invasively. Furthermore, the key disease cell, the Th2 cell is known. We study SAR using allergen-challenged CD4+ cells from allergic patients.
2009-10-16 | GSE18574 | GEO