IL-10-produced by human transitional B-cells down-regulates CD86 expression on B-cells leading to inhibition of CD4+T-cell responses

• Published in: Scientific reports 2016-01, Vol.6 (1), p.20044-20044, Article 20044
• Main Authors: Nova-Lamperti, Estefania, Fanelli, Giorgia, Becker, Pablo D., Chana, Prabhjoat, Elgueta, Raul, Dodd, Philippa C., Lord, Graham M., Lombardi, Giovanna, Hernandez-Fuentes, Maria P.
• Format: Article
• Language: English
• Subjects: 13/31; 631/250/127/1213; 631/250/1619/40/1907; 631/250/2520; 692/4022/272; 96/21; Adult; Aged; Autocrine Communication; B7-2 Antigen - metabolism; CD4 antigen; CD4-Positive T-Lymphocytes - cytology; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; Cell growth; Cell Proliferation; Down-Regulation; Female; Healthy Volunteers; Humanities and Social Sciences; Humans; Immune Tolerance; Immunology; Interleukin-10 - biosynthesis; Kidney Transplantation; Lymphocytes T; Male; Middle Aged; multidisciplinary; Precursor Cells, B-Lymphoid - metabolism; Science; T cell receptors; Young Adult
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep20044

A novel subset of human regulatory B-cells has recently been described. They arise from within the transitional B-cell subpopulation and are characterised by the production of IL-10. They appear to be of significant importance in regulating T-cell immunity in vivo . Despite this important function, the molecular mechanisms by which they control T-cell activation are incompletely defined. Here we show that transitional B-cells produced more IL-10 and expressed higher levels of IL-10 receptor after CD40 engagement compared to other B-cell subsets. Furthermore, under this stimulatory condition, CD86 expressed by transitional B-cells was down regulated and T-cell proliferation was reduced. We provide evidence to demonstrate that the down-regulation of CD86 expression by transitional B-cells was due to the autocrine effect of IL-10, which in turn leads to decreased T-cell proliferation and TNF-α production. This analysis was further extended to peripheral B-cells in kidney transplant recipients. We observed that B-cells from patients tolerant to the graft maintained higher IL-10 production after CD40 ligation, which correlates with lower CD86 expression compared to patients with chronic rejection. Hence, the results obtained in this study shed light on a new alternative mechanism by which transitional B-cells inhibit T-cell proliferation and cytokine production.