Extrafollicular IgD+ B cells Generate IgE Antibody Secreting Cells in the Nasal Mucosa
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ABSTRACT:
PROVIDER: PRJNA729498 | ENA |
REPOSITORIES: ENA
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Project description:Here we describe the dynamics underlying the generation of IgE-antibody secreting cells (ASC) in human nasal polyps (NP), mucosal tissues rich in ASC without germinal centers (GC). Using VH next generation sequencing, we identified an extrafollicular (EF) mucosal IgD+ naïve-like intermediate B cell population with high connectivity to the mucosal IgE ASC. Mucosal IgD+ B cells, express germline epsilon transcripts and predominantly co-express IgM. However, a small but significant fraction co-express IgG or IgA instead which also show connectivity to ASC IgE. Phenotypically, NP IgD+ B cells display an activated profile and molecular evidence of BCR engagement. Transcriptionally, mucosal IgD+ B cells reveal an intermediate profile between naïve B cells and ASC. Single cell IgE ASC analysis demonstrates lower mutational frequencies relative to IgG, IgA, and IgD ASC consistent with IgE ASC derivation from mucosal IgD+ B cell with low mutational load. In conclusion, we describe a novel mechanism of GC-independent, extrafollicular IgE ASC formation at the nasal mucosa whereby activated IgD+ naïve B cells locally undergo direct and indirect (through IgG and IgA), IgE class-switch.
2021-05-13 | GSE174349 | GEO
Project description: Not available
| S-EPMC8160425 | biostudies-literature
Project description:Here we investigate the transcriptional landscapes of nasal polyp IgD+ (naïve-like) B cells, nasal polyp ASC, and blood naïve B cells using RNA-seq. These data found that nasal polypP IgD+ naïve-like B cells are activated and similar to nasal polyp ASC and distinct from circulating B cells in the blood.
2021-05-20 | GSE174681 | GEO
Project description:This pilot study is a double-blinded, randomized controlled, two-centre trial in which subjects will receive 4 to 8 (subcutaneous administered) doses of medication (Omalizumab or placebo) (dose and dosing interval calculated on body weight and baseline total serum IgE). During the treatment period and follow-up, the clinical efficacy of the treatment will be assessed by evaluation of symptoms, Quality of Life questionnaire, morning Peak Expiratory Flow measurement, smell test, nasal endoscopy, CT-scan, peak nasal inspiratory flow and spirometry. Biological activity will be evaluated by measuring peripheral and local (in serum, in nasal secretions, biopsies) markers of inflammation.
Study hypothesis
1. Evaluation of the efficacy and safety of anti-IgE (Omalizumab) in patients with nasal polyposis and comorbid asthma.
2. Exploration of anti-IgE effects on local and systemic metabolism of IgE in nasal polyposis
3. Clinical assessment of the IgE theory in the pathogenesis of nasal polyps
| 2109692 | ecrin-mdr-crc
Project description:Transcriptome comparison of untreated murine IgD+B cell with LPS treated IgD+B cell B-lymphocytes constitute an important aspect of mammalian immune systems by virtue of their ability to produce highly specific antibodies in response to foreign antigens and pathogens. When B-lymphocytes encounter the particular antigen that they are responsive to, they differentiate into two types of cells: short-lived antibody-secreting plasma cells and long-lived memory cells. While the plasma B cells are responsible for the rapid resolution of a current infection or immune challenge, the memory B cells are responsible for mounting a rapid response to subsequent exposures. Previous work had demonstrated that treatment of mice with a single dose of anti-CD40 at the time of immunization lead to improved secondary responses, suggesting an enhancement of the memory B cell pool. We are currently studying the molecular mechanisms underlying the generation of memory B cells, using CD40 signalling as a tool. We have carried out a Microarray analyses of genome wide gene expression patterns in naïve B-lymphocytes following CD40 signalling, over multiple time points. Analysis used untreated IgD+B cells as control for comparison to LPS treated cells as test. Indirect comparisons were made across multiple arrays with raw data pulled from different channels for data analysis and comparison to the control data.
2012-12-25 | E-GEOD-30546 | biostudies-arrayexpress
Project description:RNA microarray profiling analysis was performed on splenic B cell subsets: “IgD+CD27-” (naive B cells) and “IgD+CD27+” (MZB B cells) isolated from splenic samples of 6 adults
2021-09-23 | E-MTAB-9620 | biostudies-arrayexpress
Project description:To define the global landscape of mRNA changes in anergic B cells, and how this affected by surface IgD, mature CD93-CD23+ HEL-binding B cells were sorted from spleens of independent transgenic mice of the following genotypes: MD4, naïve B cells coexpressing IgM and IgD; MD4:ML5, anergic B cells coexpressing IgM and IgD; MM4, naive B cells expressing only IgM; MM4:ML5, anergic B cells expressing only IgM; DD6, naive B cells expressing only IgD; DD6:ML5, anergic B cells expressing only IgD.
2016-09-30 | GSE82091 | GEO
Project description:RNA sequencing was performed to determine the uniqueness of splenic follicular IgD low B cells compared to splenic follicular IgD high and marginal zone B cells.
2018-12-03 | GSE111911 | 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