2016 Fiscal Year Annual Research Report
| Project/Area Number |
15F15908
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| Research Institution | Osaka University |
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Principal Investigator |
黒崎 知博 大阪大学, 免疫学フロンティア研究センター, 特任教授(常勤) (50178125)
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| Co-Investigator(Kenkyū-buntansha) |
TSAI CHAO-YUAN 大阪大学, 免疫学フロンティア研究センター, 外国人特別研究員
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| Project Period (FY) |
2015-04-24 – 2017-03-31
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| Keywords | Autophagy / Germinal center / Rubicon / B cell survival / Secretory autophagy |
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| Outline of Annual Research Achievements |
Understanding the survival control mechanism of long-lived, antibody-producing cells and memory B cells at the germinal center (GC) is required for developing a effective vaccine against various infectious diseases including influenza viruses. It is unclear whether enhanced autophagy alters GC B cell differentiation. Rubicon, an autophagy suppressor, was up-regulated in activated B cells, suggesting that Rubicon may suppress autophagy in B cells. To address these questions, we generated pan-B cell- and GC-B cell-specific Rubicon-mutant mouse, respectively. A decrease in antigen-specific high-affinity antibody production and an increase in autoantibody such as anti-DNA antibody were found in Rubicon-mutant mice, suggesting that Rubicon may play a role in the selection of antigen-specific B cell. However, a small-molecular-weight protein that seems to be a Rubicon isoform was found in Rubicon-mutant B cells, suggesting that deletion of the Rubicon gene is incomplete. Thus, it is necessary to confirm the present results and clarify the function of each isoform of Rubicon with the complete Rubicon-deficient mouse. On the other hand, we unexpectedly found that CD40 signal specifically induced the secretion of LC3-II containing exosomes, suggesting that CD40 signal is involved in secretory autophagy. In addition, such secretion was enhanced in the Rubicon-mutant cells. CD40 is an essential molecule during B cell-T cell interaction, and further study of CD40-induced secretory autophagy may reveal a novel mechanism of lymphocyte interaction via secretory autophagy or exosome.
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| Research Progress Status |
28年度が最終年度であるため、記入しない。
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| Strategy for Future Research Activity |
28年度が最終年度であるため、記入しない。
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