B細胞における抗原受容体の関与により,ファス依存型Th1媒介性アポトーシスに対する保護
T L Rothstein1, J K Wang, D J Panka
1Department of Medicine, Evans Memorial Department of Clinical Research, Boston University Medical Center, Massachusetts 02118.
Nature
|March 9, 1995
まとめ
活性化されたB細胞は,T細胞が誘発した死に対する感受性が異なっています. 免疫グロブリン受容体のシグナリングは,B細胞をFas媒介のアポトーシスから保護し,抗原特異細胞の生存を保証します.
科学分野:
- 免疫学 免疫学とは
- 細胞生物学 細胞生物学
- アポトーシス (apoptosis) とは
背景:
- 細胞毒性CD4+Tヘルパー1 (Th1) 細胞は,ファス依存経路を通じてアポトーシスを誘導する.
- 活性化されたB細胞は潜在的な標的ですが,Th1媒介の細胞毒性に対するそれらの感受性は完全に理解されていません.
- ファス媒介アポトーシスの感受性に対するB細胞刺激法の影響は,調査が必要です.
研究 の 目的:
- 細胞毒性CD4+Th1細胞によって誘発されるFas媒介アポトーシスに対するB細胞刺激のモードがB細胞の感受性に影響するかどうかを調査する.
- B細胞アポトーシスにおけるCD40リガンド (CD40L) と抗免疫グロブリンM (抗IgM) 刺激の役割を決定する.
- T細胞媒介による細胞毒性に対するB細胞耐性または感受性の基礎となるメカニズムを解明する.
主な方法:
- CD40Lと/または抗IgMと細胞毒性T細胞で刺激されたB細胞の共培養.
- Fas媒介経路を用いたB細胞アポトーシス感受性の評価.
- トランスジェニックB細胞 (3-83) と,特定のMHCクラスI発現 (H-2Kk,H-2Kb,H-2Kd) を有するスプレノサイトを用いて.
主要な成果:
- CD40Lで刺激されたB細胞は,Fas媒介によるアポトーシスに対して非常に敏感でした.
- 抗IgM刺激を受けたB細胞は,Fas媒介によるアポトーシスに対する抵抗を示した.
- CD40Lと抗IgMの両方の共刺激により,抵抗が生じ,抗IgM介護による保護が支配的で活発であることを示す.
- 耐性は,特異的なMHC-マッチしたスプレノサイトと共同培養されたとき,トランスジェニックB細胞でも観察されました.
結論:
- B細胞は,T細胞による自滅を積極的に制御することができる.
- 免疫グロブリン受容体の関与は,Fas依存アポトーシスから保護します.
- この保護は,防犯メカニズムとして作用し,傍観者B細胞を排除しながら,抗原特異性B細胞の生存を保証します.
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