ネズミの重症複合免疫不全の欠陥:信号配列の結合がV(D) J再結合のセグメントのコーディングではない

M R Lieber¹, J E Hesse, S Lewis

¹Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland 20892.

Cell

|October 7, 1988

まとめ

重症複合免疫不全 (scid) のマウスは,異常なV(D) J再結合を示しています. このコードの末端結合の欠陥は,免疫グロブリンとT細胞受容体の生成を妨げ,免疫不全を説明します.

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:

重症複合免疫不全 (SCID) は,Tリンパ球とBリンパ球の両方の深刻な欠陥によって特徴づけられる遺伝疾患のグループです.
V(D) J再結合プロセスは,免疫グロブリンとT細胞受容体を含む抗原受容体の多様性を生成するために不可欠です.

研究の目的:

SCIDマウスのV(D) J再結合欠陥の背後にある分子メカニズムを調査する.
SCID前B細胞とT細胞におけるコードエンド結合の失敗が,機能的な抗原受容体の欠如を説明するかどうかを判断する.

主な方法:

スキッド・マウスからのプレ-Bとプレ-T細胞系をV(D) J再結合信号配列を含むプラズミッドで変異させる.
信号末端結合とコーディング末端結合を評価するために回収されたプラズミドの分析.
リコンビネーション中のニュクレオチド除去と逆転の評価.

主要な成果:

シグナル端はシド細胞で結合されたが,約半数の再結合体では異常な核酸欠損があった.
コディングの末端は,消去反応と逆転反応V (((D)) J再結合反応の両方で結合できませんでした.
符号の末端は,代替の非V (((D)) J再結合経路に参加することが観察されました.

結論:

関節形成のコーディングの失敗は,シド前B細胞と前T細胞のV(D) J再結合の主要な欠陥です.
この欠陥は,免疫グロブリンとT細胞受容体発現の欠如を十分に説明する.
このメカニズムを理解すると,リンパ球の発達と免疫システムの機能の洞察が得られます.

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