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微生物の植民地化は,腸内膜 (lamina propria) の早期のB系統の発達に影響を与えます

Duane R Wesemann¹, Andrew J Portuguese, Robin M Meyers

¹Program in Cellular and Molecular Medicine and Department of Medicine, Children's Hospital Boston, Boston, Massachusetts 02115, USA. dwesemann@research.bwh.harvard.edu

|August 23, 2013

まとめ

B細胞の発達は,マウスの腸内ラミナプロピアで起こります,骨髄だけではありません. V(D) J再結合と受容体編集を含むこの腸に関連したB細胞の発達は,腸の微生物によって影響を受け,抗体レパートリーを形成します.

科学分野:

免疫学免疫学とは
発達生物学発達生物学とは
マイクロバイオーム研究

背景:

RAG1/RAG2内核酵素 (RAG) は,V(D) J再結合において決定的な役割を果たし,免疫グロブリン遺伝子を組み立て,抗体の多様性を生み出します.
主要なB細胞の発達と免疫グロブリンレパートリーの多様化は,主に骨髄で起こります.
未成熟のB細胞における受容体編集は,継続的なRAG発現を伴うが,抗原との遭遇に対応して抗体の特異性を精製する.

研究の目的:

早期のB細胞発達が外骨格部位,特にマウスの腸内板状 (LP) に発生するかどうかを調査する.
V(D) J再結合と受容体編集プロセスがLP内の免疫グロブリンレパートリーを調節するかどうかを決定する.
腸関連B細胞の発達と免疫グロブリンレパートリーに対する共生微生物の影響を調査する.

主な方法:

離乳年齢のマウスの腸内膜 (LP) のB系細胞の分析.
LPB系細胞におけるRAG発現とV(D) J再結合中間物質の検出.
LPと骨髄B系統細胞のVHとVκレパートリーの比較.
腸内微生物群で植民された無菌マウスにおけるB細胞発育と免疫グロブリン発現 (Igκ vs. Igλ) の評価.

主要な成果:

マウスLPでは,RAG発現するB系細胞とpro-B,pre-B,および編集フェノタイプが同定されました.
LP B系統の細胞は,骨髄の細胞とは異なる,進行中のV(D) J再結合と受容体編集を示した.
LPB系統細胞は,VHレパートリーに類似しているが,骨髄細胞と比較してVκレパートリーが有意に異なる.
細菌のないマウスのコロニー化は,特にLPでB細胞比を表すIgλからIgκの増加をもたらしました.

結論:

早期のB細胞発達は,腸内粘膜,特に自己膜 (lamina propria) の内部で起こります.
V(D) J再結合とLPにおける受容体編集は,腸のプライマリ免疫グロブリンレパートリーを調節する.
開始微生物からの細胞外信号は,腸関連B細胞の発達を調節し,免疫グロブリンレパートリーに影響を与えます.

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