B regulatory cells are increased in hypercholesterolaemic mice and protect from lesion development via IL-10

Summary Whilst innate B1-B cells are atheroprotective, adaptive B2-B cells are considered pro-atherogenic. Different subsets of B regulatory cells (Breg) have been described. In experimental arthritis and lupus-like disease, Breg are contained within the CD21hiCD23hiCD24hi B cell pool. The existence and role of Breg in vascular disease is not known. We sought to investigate the existence, identity and location of Breg 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 CD21hiCD23hiCD24hi B cells are unexpectedly increased in the draining LNs of ApoE-/- mice. Adoptive transfer of LN-derived B2-B cells or purified CD21hiCD23hiCD24hi 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-Breg subset that confers IL-10 mediated protection from neointima formation. This may open the way for immune modulatory approaches in cardiovascular disease.