title: IL-10 production in murine IgM+CD138hicells is driven by Blimp-1 and downregulated in class-switched cells.
abstract: In contrast to antibody-induced inflammatory responses, some B-cell subpopulations suppress inflammation through the production of interleukin (IL)-10. However, the mechanisms underlying Il10 gene expression during B-cell development is elusive. Here, we identify IgM+B220loCD138hicells responsible for marked IL-10 production in the bone marrow and spleen of mice. These murine IL-10-producing cells predominantly secrete IgM and have unique characteristics of long-lived plasma cells in spite of high expression of surface IgM. We found that IL-10 production is strongly correlated with the expression level of Prdm1 (encoding the Blimp-1 protein), an essential regulator of plasma cell development. Furthermore, overexpression of Prdm1 induces Il10 expression in naïve 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+CD138hicells without class-switching elicits IL-10 production. Adoptive transfer of Il10-deficient B cells into B-cell-deficient mice demonstrated that IgM+CD138hicell-derived IL-10 supports the survival of class-switched plasma cells and their antibody production in response to antigen challenge. These findings reveal an important role for IL-10 secretion by IgM+CD138hicells in the complete and efficient humoral response.
authors.affiliation: Department of Immune Regulation, Research Center for Hepatitis and Immunology, Research Institute, National Center for Global Health and Medicine, Ichikawa, Chiba, Japan.
authors.forename: Nao
authors.initials: N
authors.lastname: Suzuki-Yamazaki
authors.affiliation: Department of Laboratory Animal Medicine, Research Institute, National Center for Global Health and Medicine, Shinjuku, Tokyo, Japan.
authors.forename: Rieko
authors.initials: R
authors.lastname: Yanobu-Takanashi
authors.affiliation: Department of Laboratory Animal Medicine, Research Institute, National Center for Global Health and Medicine, Shinjuku, Tokyo, Japan.|Section of Animal Models, Department of Infectious Diseases, Research Institute, National Center for Global Health and Medicine, Shinjuku, Tokyo, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Okamura
authors.affiliation: Department of Immune Regulation, Research Center for Hepatitis and Immunology, Research Institute, National Center for Global Health and Medicine, Ichikawa, Chiba, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Takaki
mesh_terms: D000818:Animals; D000917:Antibody Formation / Q000235:genetics; D001402:B-Lymphocytes / Q000502:physiology*; D002454:Cell Differentiation / Q000235:genetics; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D017578:Immunoglobulin Class Switching; D007075:Immunoglobulin M / Q000378:metabolism; D016130:Immunophenotyping; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism*; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010950:Plasma Cells / Q000502:physiology*; D000074462:Positive Regulatory Domain I-Binding Factor 1; D053668:Syndecan-1 / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: C556062:IL10 protein, mouse; D007075:Immunoglobulin M; C513258:Prdm1 protein, mouse; D053668:Syndecan-1; D014157:Transcription Factors; D016753:Interleukin-10; D000074462:Positive Regulatory Domain I-Binding Factor 1; D017493:Leukocyte Common Antigens
keywords: B cell; Blimp-1; Immunoglobulin class-switch recombination; Interleukin-10; Plasmablast