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Whilst innate B1-B cells are atheroprotective, adaptive B2-B cells are considered pro-atherogenic. Different subsets of B regulatory cells (B(reg)) have been described. In experimental arthritis and lupus-like disease, B(reg) are contained within the CD21(hi)CD23(hi)CD24(hi) B cell pool. The existence and role of B(reg) in vascular disease is not known. We sought to investigate the existence, identity and location of B(reg) in vascular disease. The representation of B2-B cell subsets in the spleens and lymph nodes (LNs) of Apolipoprotein E(-/-) (ApoE(-/-)) mice compared to controls was characterised by flow cytometry. Additionally, we utilised a model of neointima formation based on the placement of a perivascular collar around the carotid artery in ApoE(-/-) mice to ascertain whether B cells and B cell subsets confer protection against lesion development. Adoptive transfer of B cells was performed from wild type or genetically modified mice. We showed that CD21(hi)CD23(hi)CD24(hi) B cells are unexpectedly increased in the draining LNs of ApoE(-/-) mice. Adoptive transfer of LN-derived B2-B cells or purified CD21(hi)CD23(hi)CD24(hi) B cells to syngeneic mice reduced lesion size and inflammation without changing serum cholesterol levels. Follicular B2-B cells did not confer protection. IL-10 blockade or transfer of IL10-deficient B cells prevented LN-derived B cell-mediated protection. This is the first identification of a specific LN-derived B2-B(reg) subset that confers IL-10 mediated protection from neointima formation. This may open the way for immune modulatory approaches in cardiovascular disease.

Original publication

DOI

10.1160/TH14-12-1084

Type

Journal

Thromb Haemost

Publication Date

10/2015

Volume

114

Pages

835 - 847

Keywords

B regulatory cells, Immunity, atherosclerosis, interleukins, vascular disease, Adaptive Immunity, Adoptive Transfer, Animals, Antigens, CD24, Antigens, CD40, Apolipoproteins E, B-Lymphocyte Subsets, Carotid Arteries, Carotid Artery Diseases, Carotid Artery Injuries, Cell Proliferation, Cells, Cultured, Disease Models, Animal, Female, Genotype, Hypercholesterolemia, Interleukin-10, Lymph Nodes, Lymphocyte Activation, Mice, Inbred C57BL, Mice, Knockout, Neointima, Phenotype, Protective Factors, Receptors, Complement 3d, Receptors, IgE, Signal Transduction, T-Lymphocytes, Regulatory, Time Factors