Identification of mechanisms for IL-10 production by regulatory B cells

2016 Fiscal Year Final Research Report

• Project/Area Number: 25860800
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Hematology
• Research Institution: National Center for Global Health and Medicine
• Principal Investigator: Yamazaki Nao (鈴木奈穂) 国立研究開発法人国立国際医療研究センター, 免疫制御研究部, 上級研究員 (20646848)
• Project Period (FY): 2013-04-01 – 2017-03-31
• Keywords: B細胞 / 形質細胞 / IL-10

Outline of Final Research Achievements

We have identified a new population of phenotypic IgM+B220loCD138hi cells responsible for marked IL-10 production in murine bone marrow and spleen. These cells predominantly secreted IgM and had characteristics of long-lived plasma cells. We found that IL-10 production was strongly correlated with the expression level of Prdm1 (encoding the Blimp-1 protein), an essential regulator of plasma cell development. Furthermore, transduction of Prdm1 induced Il10 expression in naive B cells. Immunoglobulin class-switching recombination events resulted in the downregulation of both Il10 and Prdm1 expression in differentiating B cells. Thus, the prolonged elevation of Blimp-1 expression during the formation of IgM+CD138hi cells without class-switching elicited IL-10 production. Adoptive transfer of Il10-deficient B cells into B cell-deficient mice demonstrated that IgM+CD138hi cell-derived IL-10 supported class-switched plasma cells and their antibody production in response to antigen challenge.

Free Research Field

免疫学