MDA-LDL vaccination induces athero-protective germinal center-derived antibody responses

Abstract

ABSTRACTAtherosclerosis is a chronic inflammatory disease of the arteries that can lead to thrombosis, infarction and stroke and is the leading cause of mortality worldwide. Immunization of pro-atherogenic mice with malondialdehyde-modified low-density lipoprotein (MDA-LDL) neo-antigen is athero-protective. However, the immune response to MDA-LDL and the mechanisms responsible for this athero-protection are not completely understood. Here, we find that immunization of mice with MDA-LDL elicits memory B cells, plasma cells, and switched anti-MDA-LDL antibodies as well as clonal expansion and affinity maturation, indicating that MDA-LDL triggers a bona fide germinal center antibody response. Further, Blimp1-deficient pro-atherogenic chimeras lacking germinal center-derived plasma cells, show accelerated atherosclerosis. Finally, we show that MDA-LDL immunization does not promote athero-protection in mice lacking germinal-center derived plasma cells, indicating that germinal center-derived antibodies are important for MDA-LDL-driven athero-protection. These findings support the idea that MDA-LDL-based vaccines could potentially be used for the prevention or treatment of atherosclerosis.