Pax5発現の喪失時にB細胞のコミットメントの逆転
Ingvild Mikkola1, Barry Heavey, Markus Horcher
1Research Institute of Molecular Pathology, Vienna Biocenter, Dr. Bohr-Gasse 7, A-1030 Vienna, Austria.
Science (New York, N.Y.)
|July 6, 2002
まとめ
転写因子Pax5はB細胞の発達に不可欠である. その継続的な発現は,B細胞の結合を維持するために必要であり,初期のB細胞が他の血液細胞タイプになるのを防ぐ.
科学分野:
- 免疫学 免疫学とは
- 発達生物学 発達生物学とは
- ヘマトポエーシス (血液形成) とは
背景:
- 転写因子Pax5はB細胞系統へのコミットメントを開始する.
- B細胞の結合を維持するPax5の役割は十分に理解されていません.
研究 の 目的:
- 開発初期にB細胞系統へのコミットメントを維持するPax5の役割を調査する.
- B細胞の同一性のためにPax5が継続的に必要かどうかを判断する.
主な方法:
- コミットしたプロB細胞におけるPax5遺伝子の条件付き不活性化.
- マクロファージの潜在能力を評価するためのインビトロ分化アッセイ.
- RAG2-/-マウスの体内溶解試験で,T細胞の発達能力を評価する.
主要な成果:
- プロB細胞における条件付きPax5不活性化により,B細胞転写プログラムの開始と維持が失われました.
- Pax5欠乏のプロB細胞は, in vitro でマクロファージに微分する能力を回復しました.
- これらの細胞は,RAG2-/-マウスにおけるT細胞発育を in vivo で再構成することもできる.
結論:
- B細胞系統へのコミットメントを維持するために,Pax5の発現が継続的に求められます.
- Pax5の喪失は,コミットされたプロB細胞を,多系統化の可能性のある血液形成的祖先に変換する.
- Pax5は,発達初期にB細胞の同一性を維持するために不可欠です.
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