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- Title
IL‐10‐producing B cells are characterized by a specific methylation signature.
- Authors
Tonon, Silvia; Mion, Francesca; Dong, Jun; Chang, Hyun‐Dong; Dalla, Emiliano; Scapini, Patrizia; Perruolo, Giuseppe; Zanello, Andrea; Dugo, Matteo; Cassatella, Marco A.; Colombo, Mario P.; Radbruch, Andreas; Tripodo, Claudio; Pucillo, Carlo E.
- 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.
- Subjects
B cells; CHRONIC lymphocytic leukemia; MANTLE cell lymphoma; DNA fingerprinting; METHYLATION; DNA methyltransferases
- Publication
European Journal of Immunology, 2019, Vol 49, Issue 8, p1213
- ISSN
0014-2980
- Publication type
Article
- DOI
10.1002/eji.201848025