北村研究室Kitamura Lab.

北村 大介 教授Daisuke Kitamura
北村研究室Kitamura Lab.
研究分野Research Area
分子免疫学Molecular Immunology
研究テーマResearch theme
in vitroにおける抗原特異的B細胞の選択と抗体の作製方法の開発



免疫記憶の形成は、一歩間違うとアレルギーを引き起こす!? 抗原に出あったリンパ球B細胞は、ヘルパーT細胞(TH)から刺激を受けて増殖する間に抗原受容体のクラススイッチ(IgM型からIgG型へ)を起こし、胚中心を形成する。胚中心B細胞では、抗原受容体(および抗体)の遺伝子に突然変異が蓄積し、その結果、抗原受容体が多様化したB細胞の中から抗原に強く結合するものが選択される。それらは記憶B細胞や長期生存プラズマ細胞へと分化し、免疫記憶を担う。IgG型の胚中心B細胞や記憶B細胞の一部がさらにクラススイッチを起こして長期にIgE抗体を産生するようになると、アレルギーを起こす可能性がある。このような免疫記憶の形成やその制御異常によるIgEの長期産生の分子メカニズムを研究している。

Daisuke Kitamura Professor

Labo’s Website

Kitamura Lab.
Research Category
Division of Molecular Biology
Research theme
Mechanisms of differentiation and maintenance of memory B cells and LLPCs.
Mechanisms regulating somatic hypermutation and selection of germinal center B cells.
Mechanisms regulating the fate of IgE+ B cells.
Mechanisms of the development and function of regulatory B cells.
Mechanisms of B cell receptor signal transduction.
Development of in vitro systems to select antigen-specific B cells.
Development of a new anti-tumor therapy using autologous plasma cells.

Our research has recently focused on B cell immune responses and the mechanisms of B cell diversification, selection, and differentiation in germinal centers (GC). To study these events at the molecular level, we have established a culture system in which cells with a GC-B cell phenotype are able to proliferate extensively, and, depending on the culture conditions, undergo class switching and differentiate into precursors of memory B cells, long-lived plasma cells (LLPCs), or regulatory B (Breg) cells that are able to survive and function in vivo. This culture system is useful for investigating several outstanding questions in B cell biology, including the mechanism for AID-mediated hypermutation of immunoglobulin V region genes, the requirements for affinity selection, the identity of the transcription factors that determine the differentiation of GC B cells into memory B cells, LLPCs and Breg cells, the microenvironment and factors required for the longevity and function of the same cells, and the signaling events and outcomes of IgG and IgE isotype B cell receptor engagement. In addition, we are exploiting this culture method to develop an in vitro system to expand rare antigen-specific B cells from human blood. In the near future, these cells will be transferred into cancer patients to generate anti-tumor antibody-producing LLPCs in vivo, or to generate human monoclonal antibodies in vitro.