Elucidation of diverse response mechanisms of activated B cells by single cell analysis

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K06480
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 43010:Molecular biology-related
• Research Institution: Tohoku University
• Principal Investigator: MUTO Akihiko 東北大学, 医学系研究科, 准教授 (80343292)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: B細胞 / Bach2

Outline of Final Research Achievements

In B cell immune response, antigen-activated B cells select their cell fate from multiple outcomes. The heterogeneity in cell fate decisions is regulated by the integration of extrinsic and intrinsic factors. However, specific intrinsic regulators and their coordinated functions are unclear. Several transcription factors have been implicated as intrinsic regulators, and one major unanswered question is how these factors regulate cell fate decision at the single-cell level. Flowcytometric analysis of reporter mice, which indicate Bach2 expression via RFP fluorescence, demonstrate that stochastic expression of Bach2 works as a cell intrinsic factor providing heterogeneity to individual B cells. Single cell PCR analysis indicate that Bach2 expression levels can influence the probability for B cell fate decision. Our study reveals an intrinsic molecular mechanism for the regulation of activated B cell fate decision.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

免疫応答を担うBリンパ球（B細胞）は、抗原で活性化されると抗体を分泌する形質細胞へ分化するのか、抗体のアイソタイプをデフォルトのIgMからIgGやIgAもしくはアレルギーの原因となるIgEに変更するクラススイッチをおこなうのか、免疫記憶を担うメモリーB細胞に分化するのか、さらに抗体の抗原に対する結合能（親和性）を上げるために胚中心B細胞に分化するのかという複数の細胞運命から選択する。しかし、この細胞運命決定がどの様なメカニズムで規定されるのかは不明であった。本研究では転写因子Bach2が確率的に決定される細胞運命の細胞自身の内的要因である可能性を見出した。