Ｂリンパ球の分化と自己免疫に関するマウスｇｐ４９Ｂの機能解析

2017 Fiscal Year Annual Research Report

• Project/Area Number: 16J01922
• Research Institution: Tohoku University
• Principal Investigator: WONG YI LI 東北大学, 生命科学研究科, 特別研究員(DC1)
• Project Period (FY): 2016-04-22 – 2019-03-31
• Keywords: glycoprotein 49B / SLE / pathogenic antibody

Outline of Annual Research Achievements

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.

Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

Early establishment of gp49B-knockout in FcgammaRIIB-knockout SLAM129 mice allowed long term monitoring (nearly one year) of mice in developing autoimmune disease accompanied with aging. Association of gp49B with SLE disease onset in aged mice was observed.

Strategy for Future Research Activity

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.