Elucidation of the cause of allergy by identifying somatic mutations in human IgE+ memory B cells.
| Project/Area Number |
18K16162
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 54020:Connective tissue disease and allergy-related
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| Research Institution | National Center for Global Health and Medicine |
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Principal Investigator |
Nguyen Tien Dat 国立研究開発法人国立国際医療研究センター, その他部局等, 上級研究員 (50750270)
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| Project Period (FY) |
2018-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | Allergy / B cells / IgE / アレルギー |
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| Outline of Final Research Achievements |
I have developed a system to selectively expand IgE+ B cells by a four-step B cell culture procedure. Starting with blood B cells of hay fever allergic donors, we successfully obtained almost pure population of IgE+ B cells with this procedure in combination with cell sorting. Exome analysis of the patients’ IgE+ B cells revealed various somatic mutations, which may be the cause of membrane IgE endocytosis defect of the patients’ IgE+ B cells. We have also identified 2 species of mRNA of membrane-bound εH chain: one encoding the conventional εH chain with an extracellular membrane-proximal domain (EMPD) and transmembrane domains, and the other lacking these domains but containing C-terminal peptide with a shifted reading frame, termed IgE-NET. The IgE-NET facilitated spontaneous plasma-cell differentiation and apoptosis of IgE+ B cells more than conventional IgE, and thus may contribute to the regulation of IgE+ B cells and of IgE synthesis in allergic disease.
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| Academic Significance and Societal Importance of the Research Achievements |
Membrane IgE endocytosis is defective in allergic donor-derived B cells, leading to high IgE expression, possibly due to somatic mutation of endocytosis-related genes. New IgE isoform facilitated spontaneous plasma-cell differentiation and apoptosis of IgE+ B cells more than conventional IgE.
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Report
(3 results)
Research Products
(5 results)
