LAUSR

The cardiovascular system is subject to hyperlipidaemic, inflammatory, and pro-oxidant stressors. Over time, these factors drive prevalent chronic diseases, of which atherosclerosis is most prominent and accounts for the majority of deaths globally. Antibody-producing B cells perform a unique role in responses to stress, injury, and infection. The power, inducibility, and adaptability of the antibody repertoire require an equally complex range of control measures. Defects and chronic perturbations in these checkpoints lead to inappropriate antibody responses, which might have important roles in shaping the development and outcome of atherosclerotic disease. A unique aspect related to atherosclerosis is the prominent role of natural antibodies, specifically those binding to the oxidized epitopes that are abundant on modified lipoproteins and cellular debris. B cells control cellular immune responses through cell–cell contact, antigen presentation, and cytokine production, and thereby participate in systemic and local immune responses in atherosclerotic arteries. To date, both proatherogenic and antiatherogenic properties have been assigned to B cells, depending on subsets and how they are functionally targeted. For these reasons, a deeper understanding of how B cells influence atherosclerotic plaque development is being pursued with the hope of providing novel B cell-targeted interventions to prevent inflammation-driven cardiovascular events.Antibody-producing B cells perform a unique role in responses to stress, injury, and infection. In this Review, Sage and colleagues discuss the spectrum of B cell involvement in dyslipidaemia and atherosclerotic plaque development.Key pointsAtherosclerosis is associated with both innate and adaptive immune responses.Inflammation in atherosclerosis is mainly driven by neo (self-)epitopes present on LDL and dying cells, which are both recognized by natural antibodies.B cell responses targeting oxidation-specific epitopes might limit disease, whereas other antibodies might have pathogenic consequences.Antibody-independent roles for B cells, such as cytokine production and T cell regulation, also contribute to B cell control of atherosclerosis.B cell-depletion therapies and vaccination strategies show promise; however, more-precise targeting of different B cell functions is an important future goal.