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

Cell Reports, ISSN: 2211-1247, Vol: 41, Issue: 2, Page: 111468
2022
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Article Description

Atherosclerosis 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, Prdm1 fl/fl Aicda -Cre +/ki Ldlr −/− pro-atherogenic chimeras, which lack germinal center-derived plasma cells, show accelerated atherosclerosis. Finally, we show that MDA-LDL immunization is not athero-protective in mice lacking germinal-center-derived plasma cells. Our findings give further support to the development of MDA-LDL-based vaccines for the prevention or treatment of atherosclerosis.

Bibliographic Details

Martos-Folgado, Inmaculada; Del Monte-Monge, Alberto; Lorenzo, Cristina; Busse, Christian E; Delgado, Pilar; Mur, Sonia M; Cobos-Figueroa, Laura; Escolà-Gil, Joan C; Martín-Ventura, Jose L; Wardemann, Hedda; Ramiro, Almudena R

Elsevier BV

Biochemistry, Genetics and Molecular Biology

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