SCIDの欠陥は,免疫グロブリンVDJの再結合酵素機構の最終段階に影響する
Barbara A Malynn1, T Keith Blackwell, Gabrielle M Fulop
1Howard Hughes Medical Institute, New York, New York.
Cell
|August 12, 1988
まとめ
重症複合免疫不全症 (SCID) のマウスのB細胞は,遺伝子セグメントを再配置できますが,それらに結合することはできません. SCIDの欠陥は,前駆性リンパ球が分裂変異領域の遺伝子セグメントを結合できないことにある.
科学分野:
- 免疫学 免疫学とは
- 分子生物学は分子生物学である.
- 遺伝学 遺伝学とは
背景:
- アベルソン・マウリン白血病ウイルス (A-MuLV) は前駆体Bリンパ球を変異させる.
- 重症複合免疫不全症 (SCID) のマウスは,適応免疫の欠陥を示しています.
- 免疫グロブリン (Ig) 重鎖変異領域の遺伝子再編成は,B細胞の発達に不可欠です.
研究 の 目的:
- A-MuLV変異したSCIDマウス前駆体Bリンパ球におけるIg重鎖遺伝子の再配列を調査する.
- SCID B細胞のV(D) J再結合における特定の欠陥を特定するために.
主な方法:
- SCIDマウスからのA-MuLVトランスフォーマー前駆体Bリンパ球の培養.
- Ig重鎖変異領域の遺伝子再配列の分析.
- 再配列部位におけるDNA配列の結合の詳細な分析.
主要な成果:
- SCID前駆体B細胞は,Ig重鎖遺伝子セグメントを活性的に再配置し,DJHとVDJの中間物質を形成する.
- SCID pre-B細胞のVDJ再結合酵素は,再結合信号の配列を正しく認識し,DNAを分割する.
- 再配置関節の分析は,VDJ再結合酵素による正確な内核分解分裂を示しています.
結論:
- B細胞の発達におけるSCIDの欠陥は,DNA分裂ではなく,DNA結合にある.
- SCIDの前駆性リンパ球は,変異領域の遺伝子セグメントの割れたコーディング端を正しく結合することができません.
- この遺伝子セグメントの結合不能は,SCIDマウスにおける機能的なB細胞レパートリーの生成を阻害する.
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