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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.

Author information

1
Department of Immune Regulation, Research Center for Hepatitis and Immunology, Research Institute, National Center for Global Health and Medicine, Ichikawa, Chiba, Japan.
2
Department of Laboratory Animal Medicine, Research Institute, National Center for Global Health and Medicine, Shinjuku, Tokyo, Japan.
3
Section of Animal Models, Department of Infectious Diseases, Research Institute, National Center for Global Health and Medicine, Shinjuku, Tokyo, Japan.

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+ 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.

KEYWORDS:

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

PMID:
28012163
DOI:
10.1002/eji.201646549
[Indexed for MEDLINE]
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