| 研究実績の概要 |
gp49B deficiency in FcgammaRIIB-knockout SLAM129 (RIIB-/-) mice did not affect the number and frequency of plasma cells in the spleen and bone marrow. However, a reduction of anti-dsDNA IgG-secreting plasma cells was observed in gp49B-/- RIIB-/- mice by ELISpot assay.
Sera from gp49B+/+ or gp49B-/- RIIB-/- mice were collected to determine titer of anti-dsDNA IgG by ELISA. At 36-week old (which marks the onset of SLE-like disease), the titer of anti-dsDNA IgG in gp49B-/- RIIB-/- mice was significantly lower. This suggests that gp49B is involved in the initiation of disease in SLE-prone RIIB-/- mice.
Spleen memory B cells from RIIB-/- mice were stimulated in vitro to differentiate into plasmablasts. But gp49B-/- has no significant effect in reducing anti-dsDNA IgG secretion in this culture.
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| 今後の研究の推進方策 |
To elucidate the mechanism of gp49B in the development of anti-dsDNA IgG secreting plasma cells, memory B cells were first targeted as the source for differentiation into plasmablasts in vitro by CpG stimulation. However, the effect of gp49B was not clearly demonstrated. To overcome this, naive B cells will be stimulated by TLR ligand(s), IL-4, CD40 ligand and anti-IgM to simulate germinal center reaction in vitro, to identify the involvement of gp49B in B cell development.
gp49B-knockout in BXSB/Yaa mice is ready to be analyzed onwards. Preliminary findings on BXSB/Yaa mice showed that gp49B was expressed on splenic plasma cells and long-lived bone marrow plasma cells. Future works on the mechanism gp49B on plasma cells will be on apoptosis studies by in vitro means.
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