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

Cell Rep. 2022 Oct 11;41(2):111468. doi: 10.1016/j.celrep.2022.111468.

Abstract

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, Prdm1fl/flAicda-Cre+/kiLdlr-/- 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.

Keywords: B cell; CP: Immunology; MDA-LDL; antibody; atherosclerosis; germinal center; vaccine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibody Formation
  • Atherosclerosis* / prevention & control
  • Germinal Center
  • Lipoproteins, LDL
  • Malondialdehyde / pharmacology
  • Mice
  • Vaccination
  • Vaccines*

Substances

  • Lipoproteins, LDL
  • Vaccines
  • Malondialdehyde