Understanding the role of B cells in atherosclerosis: potential clinical implications

Abstract

Atherosclerosis is a progressive inflammatory disease of the medium to large arteries that is the largest contributor to cardiovascular disease. B-cell subsets have been shown in animal models of atherosclerosis to have both atherogenic and atheroprotective properties. In this review, we highlight the research that developed our understanding of the role of B cells in atherosclerosis both in humans and mice. From this we discuss the potential clinical impact B cells could have both as diagnostic biomarkers and as targets for immunotherapy. Finally, we recognize the inherent difficulty in translating findings from animal models into humans given the differences in both cardiovascular disease and the immune system between mice and humans, making the case for greater efforts at addressing the role of B cells in human atherosclerosis.

Keywords::

• atherosclerosis
• B cells
• immune modulation
• natural antibodies
• rituximab

Financial & competing interests disclosure

S Morris-Rosenfeld is funded by NIH T32 GM007267. CA McNamara is funded by R01 HL107490, P01 HL55798 and an Investigator-Initiated Grant from AstraZeneca. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Recent findings in human studies have shown that B-cell activation is strongly linked to cardiovascular disease.

• B cells aggregate at sites of lesion formation primarily in the adventitia.

• Research in animal models of atherosclerosis has demonstrated that B-cell subsets have distinct roles with innate B1 B cells having atheroprotective functions and adaptive B2 B cells having atherogenic functions though this may be too simplistic of an understanding.

• Circulating immunoglobulins and surface markers on peripheral B cells have the potential to be used as novel biomarkers of cardiovascular disease.

• A meta-analysis of B-cell depletion therapy in rheumatological diseases does not associate with short-term cardiovascular events.

• There is great potential in the use of immunization therapy to vaccinate against atherogenic antigens such as those expressed on modified low-density lipoprotein.

Notes