# Understanding IgE Biology > **NIH NIH R56** · BRIGHAM AND WOMEN'S HOSPITAL · 2021 · $300,000 ## Abstract Project Summary IgE-mediated allergic disease is a growing problem. The pathogenesis of allergic disease requires that immunoglobulin (Ig) E (IgE) molecules be produced against what are otherwise usually innocuous substances. Upon activation in the setting of cytokines such as IL-4 or IL-13, B cells can undergo IgH CSR to IgE. IgE secreted from B lineage cells can, in the presence of cognate antigen, activate mast cells and basophils to release potent inflammatory mediators. While IgE responses can lead to protective immunity as a part of a specialized responses to multicellular pathogens or other noxious threats, they also underlie allergic disease. Allergic disease can be manifest by localized inflammation, or by multiorgan involvement, including deadly systemic anaphylactic reactions via IgE-sensitized mast cell degranulation. Thus, the production and dissemination of IgE play a significant role in dictating the strength and extent of tissue mast cell sensitization. It is therefore critical to understand not only how B cell IgE production is controlled, but also the principles underlying distribution of IgE from point of origin to distal sites throughout the body. The overall objective of this application is to understand biological aspects of IgE production and dissemination and to gain insights into how this is influenced in allergic disease. Emerging literature and preliminary data from the applicant suggest a general hypothesis that biological constraints cooperate to restrict IgE dissemination under homeostatic conditions, and that accumulation of bone marrow IgE LLPCs is an aberrancy underlying systemic manifestations of allergic disease. This hypothesis will be tested by pursuing three specific aims, which are: 1) to determine the mechanisms of IgE expression dynamics on IgE B cell function; 2) to elucidate mechanisms underlying IgE distribution from point of origin to effector sites; and 3) to characterize IgE plasma cells in allergic patients. Under the first aim, IgE mRNA splicing and IgE surface density will be genetically perturbed to examine the hypothesis that mRNA production away from the mIg splice variant (i.e. the BCR variant) restricts the number and longevity IgE expressing cells, thus constraining IgE secretion largely to the insult site. Under the second aim, models of anatomic location-specific allergic challenge will be deployed to examine the degree to which IgE distribution is locally biased, and the role of B cells in this process. Under the third aim, bone marrow aspirations from healthy and allergic individuals will be obtained for IgH isotype-resolved deep sequencing as well as single cell transcriptomics to elucidate the cellular sources and biological properties of IgE in patients with long-standing severe allergies. This contribution is significant because it is expected to elucidate a more complete picture of how IgE responses are regulated. Ultimately, such knowledge has the potential to inform the developmen... ## Key facts - **NIH application ID:** 10396243 - **Project number:** 1R56AI158811-01 - **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL - **Principal Investigator:** Duane R. Wesemann - **Activity code:** R56 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2021 - **Award amount:** $300,000 - **Award type:** 1 - **Project period:** 2021-07-01 → 2022-03-09 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/10396243 ## Citation > US National Institutes of Health, RePORTER application 10396243, Understanding IgE Biology (1R56AI158811-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10396243. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*