Next Generation Sequencing Facilitates Quantitative Analysis of IgG or IgE producing B cells
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE165301 | GEO | 2021/01/23
REPOSITORIES: GEO
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Project description:Emergence of IgE antibodies that bind allergens with high affinity is highly correlated with the severity of anaphylaxis. However, the underlying molecular mechanisms by which high-affinity IgE is generated remain poorly understood. To examine function of IL-13 derived from T cells in IgE producing B cell development, we transferred IL-13 sufficient or deficient OT-2 TH2 into IgE reporter (Verigem) mice followed by immunization with NP-OVA. At 7 day post immunization, NP specific IgE producing B cells were sorted and served to single cell transcriptome analysis.
2021-01-27 | GSE165539 | GEO
Project description:We report a rare population of IL-13-producing Tfh cells that were present with high-affinity IgE to allergens. These “Tfh13” cells have an unusual cytokine profile (IL-13hiIL-4hiIL-5hiIL-21lo), co-express BCL6 and GATA3 and were required for production of high- but not low-affinity IgE and accordingly, allergen-induced anaphylaxis.
2019-08-06 | GSE132798 | GEO
Project description:Emergence of IgE antibodies that bind allergens with high affinity is highly correlated with the severity of anaphylaxis. However, the underlying molecular mechanisms by which high-affinity IgE is generated remain poorly understood. We discovered that IL-13-producing T follicular helper (TFH) cells, which we designated as TFH2 cells, are generated from conventional TH2 cells by antigen sensitization. TFH2 cells have a unique cytokine profile (IL-4+IL-5-IL-13+IL-21+) and co-express the TFH and TH2 master transcriptional regulators, BCL-6 and GATA3.
2019-09-26 | GSE137970 | GEO
Project description:Background: Most asthmatic patients have high serum levels of IgE directed against common environmental allergens such as house dust mite, animal danders and moulds. However the presence of specific IgE against individual allergens alone does not account for asthma. Many individuals are atopic but not asthmatic. Precise knowledge of the serum IgE specificity repertoire in asthmatic and non-asthmatic patients would substantially help in understanding the pathogenesis of the disease and at the same time facilitate the treatment and the implementation of preventive measures. Methods: We developed a microarray immunoassay containing 103 common allergens to study the IgE reactivity profiles of 485 asthmatic and 342 non-asthmatic individuals from families whose members had a documented history of asthma and atopy. The results were analyzed using k-means clustering to investigate whether IgE reactivity profiles correlated with asthma, disease severity and age of onset as well as with other atopic conditions such as rhinitis, conjunctivitis and eczema. We trained an artificial neural network (ANN) using the serum reactivity data to identify individuals as asthmatic and non-asthmatic. Results: Individual sera showed clear differences in the number and the combinations of allergens recognized as well as in the level of specific IgE. While the presence of specific IgE against single allergens correlated poorly with the pathological conditions examined k-means clustering analysis unraveled that a particular profile was significantly associated with asthma (p <1E-8). An ANN-based algorithm, calibrated with the profile reactivity data correctly classified as asthmatic or non-asthmatic 78% of the individual examined. Conclusions: Our analysis demonstrates that asthma may be a higher-order phenomenon related to patterns of response and not attributable to single antibody reactions. This information sheds new light on the risk of developing the disease and can be readily utilized in combination with an ANN-based tool to distinguish asthmatic and non-asthmatic individuals on the basis of their serum reactivity profile. The study consisted of a total of 872 sera samples: 485 individuals were diagnosed with asthma, 342 were classified as non asthmatic, a remaining 45 were classified as unconfirmed asthma diagnosis. The serum IgE reactivity profiles were analyzed against 103 allergens representative of 11 distinct allergen classes. Quantification of bound IgE: The fluorescence signal was acquired using ProScanArray Express™ version 3.0 software. PMC reading values of individual spots were corrected against the internal negative control to identify signals above background. Duplicate measurements of individual allergens were utilized. The signal collected from the allergens was interpolated with an external calibration curve to obtain the IU/ml value (see supplementary file GSE20020_IU_ml values.txt), and translated into a Class Score by plotting the data in a standard reactivity scale (see Sample data tables). Class Score values: (CLASS 0 (less than 0.35 IU/ml); CLASS 1 (0.35-0.7 IU/ml); CLASS 2 (0.71-3.5 IU/ml); CLASS 3 (3.51-17.5 IU/ml); CLASS 4 (17.51-50 IU/ml); CLASS 5 (50.01-100 IU/ml).
2012-01-03 | E-GEOD-20020 | biostudies-arrayexpress
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:Background: Most asthmatic patients have high serum levels of IgE directed against common environmental allergens such as house dust mite, animal danders and moulds. However the presence of specific IgE against individual allergens alone does not account for asthma. Many individuals are atopic but not asthmatic. Precise knowledge of the serum IgE specificity repertoire in asthmatic and non-asthmatic patients would substantially help in understanding the pathogenesis of the disease and at the same time facilitate the treatment and the implementation of preventive measures. Methods: We developed a microarray immunoassay containing 103 common allergens to study the IgE reactivity profiles of 485 asthmatic and 342 non-asthmatic individuals from families whose members had a documented history of asthma and atopy. The results were analyzed using k-means clustering to investigate whether IgE reactivity profiles correlated with asthma, disease severity and age of onset as well as with other atopic conditions such as rhinitis, conjunctivitis and eczema. We trained an artificial neural network (ANN) using the serum reactivity data to identify individuals as asthmatic and non-asthmatic. Results: Individual sera showed clear differences in the number and the combinations of allergens recognized as well as in the level of specific IgE. While the presence of specific IgE against single allergens correlated poorly with the pathological conditions examined k-means clustering analysis unraveled that a particular profile was significantly associated with asthma (p <1E-8). An ANN-based algorithm, calibrated with the profile reactivity data correctly classified as asthmatic or non-asthmatic 78% of the individual examined. Conclusions: Our analysis demonstrates that asthma may be a higher-order phenomenon related to patterns of response and not attributable to single antibody reactions. This information sheds new light on the risk of developing the disease and can be readily utilized in combination with an ANN-based tool to distinguish asthmatic and non-asthmatic individuals on the basis of their serum reactivity profile.
2012-01-03 | GSE20020 | GEO
Project description:Experimental IgE-mediated food allergy depends on intestinal anaphylaxis driven by interleukin (IL)-9. However, the primary cellular source of IL-9 and the mechanisms underlying the susceptibility to food-induced intestinal anaphylaxis remain unclear. Herein, we have reported the identification of multifunctional IL-9-producing mucosal mast cells (MMC9s) that can secrete prodigious amounts of IL-9 and IL-13 in response to IL-33, and mast cell protease-1 (MCPt-1) in response to antigen and IgE complex crosslinking, respectively. Repeated intragastric antigen challenge induced MMC9 development that required T cells, IL-4, and STAT6 transcription factor, but not IL-9 signals. Mice ablated of MMC9 induction failed to develop intestinal mastocytosis, which resulted in decreased food allergy symptoms that could be restored by adoptively transferred MMC9s. Finally, atopic patients that developed food allergy displayed increased intestinal expression of Il9 and MC-specific transcripts. Thus, the induction of MMC9s is a pivotal step to acquire the susceptibility to IgE-mediated food allergy. dUTP mRNA-Seq profiles of indicated hematopoietic cell lineages were generated on Illumina HiSeq2500. Hematopoietic cells were isolated from Balb/C mice that developed food allergy and bone marrow-derived mast cells were generated from naïve Balb/C mice
2015-09-11 | E-GEOD-72921 | biostudies-arrayexpress
Project description:Experimental IgE-mediated food allergy depends on intestinal anaphylaxis driven by interleukin (IL)-9. However, the primary cellular source of IL-9 and the mechanisms underlying the susceptibility to food-induced intestinal anaphylaxis remain unclear. Herein, we have reported the identification of multifunctional IL-9-producing mucosal mast cells (MMC9s) that can secrete prodigious amounts of IL-9 and IL-13 in response to IL-33, and mast cell protease-1 (MCPt-1) in response to antigen and IgE complex crosslinking, respectively. Repeated intragastric antigen challenge induced MMC9 development that required T cells, IL-4, and STAT6 transcription factor, but not IL-9 signals. Mice ablated of MMC9 induction failed to develop intestinal mastocytosis, which resulted in decreased food allergy symptoms that could be restored by adoptively transferred MMC9s. Finally, atopic patients that developed food allergy displayed increased intestinal expression of Il9 and MC-specific transcripts. Thus, the induction of MMC9s is a pivotal step to acquire the susceptibility to IgE-mediated food allergy.
2015-09-11 | GSE72921 | GEO
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:The underlying mechanisms of IgE-mediated anaphylaxis remain poorly understood. Furthermore, it remains to be determined to what extent findings from animal/mouse models reflects the pathophysiological mechanism in human. Therefore, to better characterize the mechanisms leading to potentially lethal events, analysis of global transcriptional changes (RNA-sequencing) in peripheral blood human samples in patients with anaphylaxis presenting at the emergency department and in patients with anaphylaxis during double-blind placebo-controlled food challenges (DBPCFC) to peanut, was performed. Mouse samples with different severity of IgE-mediated food-induced anaphylaxis were also included in RNA-sequencing analyses.
2022-11-21 | GSE215184 | GEO