腸の生殖中心におけるB細胞選択の調整可能な動態

Carla R Nowosad^1,2, Luka Mesin¹, Tiago B R Castro^1,2

¹Laboratory of Lymphocyte Dynamics, The Rockefeller University, New York, NY, USA.

Nature

|October 29, 2020

まとめ

腸に関連した生殖センターは,微生物なしでB細胞の選択と抗体の親和性の成熟をサポートします. 微生物群の構成はこれらの腸内構造における B細胞の選択速度を調整します

科学分野:

免疫学
微生物学
胃腸内科

背景:

生殖中心は抗体生成に不可欠ですが,通常は一時的に形成されます.
腸関連リンパ組織は,局所抗体反応を支える,慢性的に存在する生殖中心を有する.
安定状態の条件下でのB細胞選択におけるこれらの腸関連生殖センターの役割は不明である.

研究の目的:

B細胞の選択と抗体の親和性の成熟が安定状態の腸関連生殖センターで起こるかどうかを調査する.
腸内環境におけるB細胞の選択に対する微生物群の影響を決定する.

主な方法:

マウスの多彩な"ブレインボー"細胞運命をマッピングした.
単細胞から免疫グロブリン遺伝子の配列を解析した.
特定病原体フリー (SPF) と細菌フリーマウスのB細胞選択を比較した.

主要な成果:

安定状態の腸関連生殖センターの5〜10%で支配的な"勝者"B細胞クローンを特定した.
抗原によるB細胞の選択が示され,抗体は共生細菌に結合する事が示された.
精選された生殖中心のより高い頻度が細菌のないマウスで観察され,公共のクローン型が濃縮された.
微生物の植民地化は,既存のクローンタイプを排除することなく,共生性特異のB細胞反応を誘発することを示した.

結論:

B細胞のポジティブな選択は,安定状態の腸関連生殖センターで起こります.
B細胞の選択率は腸内微生物の存在と構成によって調整されます.
腸の生殖センターは,微生物群が存在しない場合でも,抗原駆動のB細胞選択を媒介することができます.

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