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

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.

• Authors: Asa C Strom, Amanda J Cross, Jennifer E Cole, Paul A Blair, Christoph Leib, Michael E Goddard, Elizabeth C Rosser, Inhye Park, Anna Hultgårdh Nilsson, Jan Nilsson, Claudia Mauri, Claudia Monaco
• Journal: Thrombosis and haemostasis (Thromb Haemost) Vol. 114 Issue 4 Pg. 835-47 (Oct 2015) ISSN: 2567-689X [Electronic] Germany
• PMID: 26063196 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Apolipoproteins E
• CD24 Antigen
• CD40 Antigens
• Cd24a protein, mouse
• IL10 protein, mouse
• Receptors, Complement 3d
• Receptors, IgE
• Interleukin-10

Topics

• Adaptive Immunity
• Adoptive Transfer
• Animals
• Apolipoproteins E (deficiency, genetics)
• B-Lymphocyte Subsets (immunology, metabolism, transplantation)
• CD24 Antigen (immunology, metabolism)
• CD40 Antigens (immunology, metabolism)
• Carotid Arteries (immunology, metabolism, pathology)
• Carotid Artery Diseases (genetics, immunology, metabolism, pathology, prevention & control)
• Carotid Artery Injuries (genetics, immunology, metabolism, pathology, prevention & control)
• Cell Proliferation
• Cells, Cultured
• Disease Models, Animal
• Female
• Genotype
• Hypercholesterolemia (complications, genetics, immunology, metabolism)
• Interleukin-10 (genetics, immunology, metabolism)
• Lymph Nodes (immunology, metabolism)
• Lymphocyte Activation
• Mice, Inbred C57BL
• Mice, Knockout
• Neointima
• Phenotype
• Protective Factors
• Receptors, Complement 3d (immunology, metabolism)
• Receptors, IgE (immunology, metabolism)
• Signal Transduction
• T-Lymphocytes, Regulatory (immunology)
• Time Factors