Abstract
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 language | English |
---|---|
Pages (from-to) | 835-847 |
Journal | Thrombosis and Haemostasis |
Volume | 114 |
Issue number | 4 |
DOIs | |
Publication status | Published - 2015 |
Subject classification (UKÄ)
- Cardiac and Cardiovascular Systems
- Immunology in the medical area
Free keywords
- Immunity
- B regulatory cells
- interleukins
- atherosclerosis
- vascular
- disease