IL-10-producing B cells are characterized by a specific methylation signature

Silvia Tonon, Francesca Mion, Jun Dong, Hyun Dong Chang, Emiliano Dalla, Patrizia Scapini, Giuseppe Perruolo, Andrea Zanello, Matteo Dugo, Marco A. Cassatella, Mario P. Colombo, Andreas Radbruch, Claudio Tripodo, Carlo E. Pucillo

Research output: Contribution to journalArticlepeer-review


Among the family of regulatory B cells, the subset able to produce interleukin-10 (IL-10) is the most studied, yet its biology is still a matter of investigation. The DNA methylation profiling of the il-10 gene locus revealed a novel epigenetic signature characterizing murine B cells ready to respond through IL-10 synthesis: a demethylated region located 4.5 kb from the transcription starting site (TSS), that we named early IL10 regulatory region (eIL10rr). This feature allows to distinguish B cells that are immediately prone and developmentally committed to IL-10 production from those that require a persistent stimulation to exert an IL-10-mediated regulatory function. These late IL-10 producers are instead characterized by a delayed IL10 regulatory region (dIL10rr), a partially demethylated DNA portion located 9 kb upstream from the TSS. A demethylated region was also found in human IL-10-producing B cells and, very interestingly, in some B-cell malignancies, such as chronic lymphocytic leukemia and mantle cell lymphoma, characterized by an immunosuppressive microenvironment. Our findings define murine and human regulatory B cells as an epigenetically controlled functional state of mature B cell subsets and open a new perspective on IL-10 regulation in B cells in homeostasis and disease.

Original languageEnglish
Pages (from-to)1213-1225
Number of pages13
JournalEuropean Journal of Immunology
Issue number8
Publication statusPublished - Jan 1 2019


  • B cells
  • B-cell malignancies
  • DNA methylation
  • epigenetics
  • Interleukin 10

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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