IL-10 production in murine IgM + CD138 hi cells is driven by Blimp-1 and downregulated in class-switched cells

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibody Formation / genetics
  • B-Lymphocytes / physiology*
  • Cell Differentiation / genetics
  • Cells, Cultured
  • Gene Expression Regulation
  • Immunoglobulin Class Switching*
  • Immunoglobulin M / metabolism
  • Immunophenotyping
  • Interleukin-10 / genetics
  • Interleukin-10 / metabolism*
  • Leukocyte Common Antigens / metabolism
  • Lymphocyte Activation / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Plasma Cells / physiology*
  • Positive Regulatory Domain I-Binding Factor 1
  • Syndecan-1 / metabolism
  • Transcription Factors / metabolism*

Substances

  • IL10 protein, mouse
  • Immunoglobulin M
  • Prdm1 protein, mouse
  • Syndecan-1
  • Transcription Factors
  • Interleukin-10
  • Positive Regulatory Domain I-Binding Factor 1
  • Leukocyte Common Antigens