ORIGINAL ARTICLE Interleukin-10 production and T cell-suppressive capacity in B cell subsets from atherosclerotic apoE -/- mice Héctor Rincón-Arévalo 1 & Janny Villa-Pulgarín 2 & Jorge Tabares 2 & Mauricio Rojas 1,3 & Gloria Vásquez 1 & José R. Ramírez-Pineda 2 & Diana Castaño 1 & Lina M. Yassin 4 # Springer Science+Business Media, LLC 2017 Abstract The evidence regarding the role of regulatory B cells (Breg) in atherosclerosis are scarce, and there are contra- dictory data about their atheroprotective properties. Due to the demonstrated protective function of Breg in different inflam- matory diseases mainly through interleukin-10 (IL-10) pro- duction, 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 vari- able 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 fre- quency 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 interfer- on 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 sug- gest that mainly FO B cells can modulate in some level the inflammatory responses observed in atherosclerosis. Keywords Regulatory B cells . Il-10 . Follicular B cells . Atherosclerosis . Apolipoprotein-E-deficient mice Introduction Cardiovascular diseases are considered a leading cause of death around the world [1]. Atherosclerosis, an inflammatory process characterized by lipid accumulation, infiltration of immune cells, and fibrous-adipose plaque formation, is the most common cause of cardiovascular diseases [2]. Multiple pieces of evidence have shown an atheroprotective role of the interleukin-10 (IL-10) produced by different immune cells [3–5]. It was reported that apolipoprotein-E-deficient (apoE -/- ) il-10 -/- mice showed higher atherosclerotic lesions Diana Castaño and Lina M. Yassin contributed equally to the present work. Electronic supplementary material The online version of this article (doi:10.1007/s12026-017-8939-6) contains supplementary material, which is available to authorized users. * Diana Castaño diana.castano@udea.edu.co * Lina M. Yassin yascatorce@yahoo.com 1 Grupo de Inmunología Celular e Inmunogenética, Instituto de Investigaciones Médicas, Facultad de Medicina, Universidad de Antioquia UdeA, Calle 70 No 52-21, Medellín, Colombia 2 Grupo Inmunomodulación, Instituto de Investigaciones Médicas, Facultad de Medicina, Universidad de Antioquia UdeA, Calle 70 No 52-21, Medellín, Colombia 3 Unidad de Citometría, Facultad de Medicina, Sede de Investigación Universitaria, Universidad de Antioquia UdeA, Calle 70 No 52-21, Medellín, Colombia 4 Grupo de Investigaciones Biomédicas Uniremington, Corporación Universitaria Remington, Medellín, Colombia Immunol Res DOI 10.1007/s12026-017-8939-6