Interleukin-10 production and T cell-suppressive capacity in B cell subsets from atherosclerotic apoE−/− mice

• Published in: Immunologic research 2017-10, Vol.65 (5), p.995-1008
• Main Authors: Rincón-Arévalo, Héctor, Villa-Pulgarín, Janny, Tabares, Jorge, Rojas, Mauricio, Vásquez, Gloria, Ramírez-Pineda, José R., Castaño, Diana, Yassin, Lina M.
• Format: Article
• Language: English
• Subjects: Allergology; Animals; Atherosclerosis - immunology; B-Lymphocyte Subsets - immunology; B-Lymphocytes, Regulatory - immunology; Biomedical and Life Sciences; Biomedicine; Cell Proliferation; Cells, Cultured; Diet, High-Fat; Disease Models, Animal; Female; Humans; Immune Tolerance; Immunology; Interferon-gamma - metabolism; Interleukin-10 - immunology; Internal Medicine; Medicine/Public Health; Mice; Mice, Inbred C57BL; Mice, Knockout, ApoE; Original Article; T-Lymphocytes - immunology; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 0257-277X; 1559-0755
• DOI: 10.1007/s12026-017-8939-6

The evidence regarding the role of regulatory B cells (Breg) in atherosclerosis are scarce, and there are contradictory data about their atheroprotective properties. Due to the demonstrated protective function of Breg in different inflammatory diseases mainly through interleukin-10 (IL-10) production, the knowledge of their participation in atherosclerosis immunopathology would be very valuable. To further study which B cell subsets participate in IL-10 production and their regulatory role, splenocytes from apolipoprotein-E-deficient mice were evaluated by ex vivo and in vitro cultures. Atherosclerotic mice had increased frequency of IL-10 + B cells, which presented high CD1d, CD19, and IgM, but variable CD5, CD21, and CD23 expression. IL-10 + B cells were not enriched in B cell subsets previously reported as Breg. Increased frequency of IL-10 + B cells with transitional 1-like (T1-like) and follicular (FO) and reduced CD5 + and marginal zone (MZ) phenotypes were observed ex vivo. Increased frequency of IL-10 + B cells with T1-like and MZ, and decreased IL-10 + FO and T2 phenotypes were also observed in vitro. To determine regulatory capacity of B cells in the atherosclerotic model, each subset were co-cultured with CD4 + CD25 − T cells. CD5 + , FO, MZ, and T1-like cells from atherosclerotic mice exhibited regulation in an IL-10-dependent manner. However, only FO cells decreased both frequency of interferon gamma (IFN-γ) + and tumor necrosis factor alpha (TNF-α) + and proliferation of T cells. Finally, splenocytes showed increased frequency of IFN-γ + and TNF-α + cells only when FO-depleted B cells were evaluated. These results suggest that mainly FO B cells can modulate in some level the inflammatory responses observed in atherosclerosis.