1. IL-10-producing B cells are characterized by a specific methylation signature.
- Author
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Tonon S, Mion F, Dong J, Chang HD, Dalla E, Scapini P, Perruolo G, Zanello A, Dugo M, Cassatella MA, Colombo MP, Radbruch A, Tripodo C, and Pucillo CE
- Subjects
- Animals, Cell Differentiation, DNA Methylation, Female, Gene Expression Profiling, Humans, Immune Tolerance, Immunity, Humoral, Lymphocyte Activation, Mice, Mice, Inbred C57BL, Tumor Microenvironment, B-Lymphocyte Subsets physiology, B-Lymphocytes, Regulatory physiology, Interleukin-10 metabolism, Leukemia, Lymphocytic, Chronic, B-Cell genetics, Lymphoma, Mantle-Cell genetics, Regulatory Sequences, Nucleic Acid genetics
- Abstract
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., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)
- Published
- 2019
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