Mechanisms for induction and regulation of memory B cell subsets exhibiting distinct recall responses

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K21533
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 49:Pathology, infection/immunology, and related fields
• Research Institution: Tokyo University of Science
• Principal Investigator: Kitamura Daisuke 東京理科大学, 研究推進機構生命医科学研究所, 教授 (70204914)
• Project Period (FY): 2020-07-30 – 2023-03-31
• Keywords: 記憶B細胞 / 免疫応答 / リコール応答 / 形質細胞 / 自己免疫疾患

Outline of Final Research Achievements

In the immune response to external antigens, responding B cells differentiate into memory B (Bmem ) cells, mostly through germinal centers (GCs), and are maintained in the body for a long period. Upon reencounter with the same antigens, Bmem cells mostly differentiate to plasma cells and produce antibodies, while some Bmem cells differentiate to GC B cells and regenerate Bmem cells, as shown in mice. The two ways of the ‘recall’ responses are mainly caused by CD80-high and CD80-low Bmem cell subsets, respectively. We recently found that differentiation toward these two subsets is determined by the strength of CD40 signaling in B cells during the primary immune response. In this study, we sought to elucidate the mechanisms for the induction, maintenance, and recall-response regulation of these Bmem cell subsets as well as of Bmem cells that generate plasma cells to produce autoantibodies in autoimmune diseases.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

本研究により、初回接種時に2つのBmem細胞サブセットの産生を調節することで、二次免疫あるいは感染時に抗体産生とBmem細胞再産生のバランスが予測できる新たなワクチンの開発が可能となる。また、自己免疫疾患において、自己反応性Bmem細胞の形質細胞への分化あるいはBmem細胞維持を阻害する治療に応用が可能となる。具体的には、自己免疫モデルマウスにおいて、自己反応性Bmem細胞が交差反応性の口腔内共生細菌に反応して形質細胞へ分化することが明らかになった。自己抗体が交差反応するこの細菌と自己抗原との共通エピトープを同定すれば、自己反応性Bmem細胞の選択的制御が可能となる。