Analysis of selection mechanisms of germinal center B cells by using a novel follicular dendritic cell line
| Project/Area Number |
23790537
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Immunology
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| Research Institution | Okayama University |
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Principal Investigator |
MAGARI Masaki 岡山大学, 大学院・自然科学研究科, 助教 (50359882)
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| Project Period (FY) |
2011 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2011: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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| Keywords | 抗体の親和性成熟 / 胚中心 / 濾胞樹状細胞 / 親和性成熟 / IL-21 |
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| Research Abstract |
In germinal centers (GCs), B cells are selected through interaction with follicular dendritic cells bearing immune complexes and follicular helper T (Tfh) cells secreting Tfh cytokines, including IL-21. To analyze these cellular interactions, we have explored culture conditions that can simulate GC B cell selection in vitro using a mouse follicular dendriticcell line, FL-YB. FL-YB cells efficiently enhanced viability of cocultured mouse B cells in a BAFF-dependent fashion. Interestingly, we found that addition of IL-21, a major Tfh cytokine, readily induced death of B cells that were cocultured with FL-YB cells, whereas IL-21 alone sustained viability of B cells in the absence of FL-YB cells. The IL-21-induced death was dependent ona low m.w. soluble factor that was released from FL-YB cells, which was finally identified as PGE2. Treatment of B cells with IL-21 plus PGE2, but not either alone, resulted in enhanced expression of a proapoptotic protein Bim and the upstream transcription factor Foxo1. A PGE2receptor isoform, EP4, was responsible for IL-21/PGE2-induced B cell death. Thus, PGE2is an endogenous chemical mediator that can switch pleiotropic actions of IL-21 on B cells. IL-21/PGE2-induced B cell death was rescued if B cells were costimulated via CD40. In immunized mice, deficiency of IL-21R in B cells led to a significant decrease in the frequency of activated caspase-3-positive GC B cells concomitant with impaired affinity maturation of Abs. Taken together, results implicate a physiological role of IL-21/PGE2-induced B cell death in GC B cell selection.
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Report
(3 results)
Research Products
(24 results)
