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Eur J Immunol. 2017 Mar;47(3):493-503. doi: 10.1002/eji.201646549. Epub 2017 Jan 10.

IL-10 production in murine IgM+ CD138hi cells is driven by Blimp-1 and downregulated in class-switched cells.

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Department of Immune Regulation, Research Center for Hepatitis and Immunology, Research Institute, National Center for Global Health and Medicine, Ichikawa, Chiba, Japan.
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.


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+ B220lo CD138hi cells 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+ CD138hi cells without class-switching elicits IL-10 production. Adoptive transfer of Il10-deficient B cells into B-cell-deficient mice demonstrated that IgM+ CD138hi cell-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+ CD138hi cells in the complete and efficient humoral response.


B cell; Blimp-1; Immunoglobulin class-switch recombination; Interleukin-10; Plasmablast

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