B Cells in Atherosclerosis: Mechanisms and Potential Clinical Applications

JACC Basic Transl Sci. 2021 Jun 28;6(6):546-563. doi: 10.1016/j.jacbts.2021.01.006. eCollection 2021 Jun.

Abstract

Because atherosclerotic cardiovascular disease is a leading cause of death worldwide, understanding inflammatory processes underpinning its pathology is critical. B cells have been implicated as a key immune cell type in regulating atherosclerosis. B-cell effects, mediated by antibodies and cytokines, are subset specific. In this review, we focus on elaborating mechanisms underlying subtype-specific roles of B cells in atherosclerosis and discuss available human data implicating B cells in atherosclerosis. We further discuss potential B cell-linked therapeutic approaches, including immunization and B cell-targeted biologics. Given recent evidence strongly supporting a role for B cells in human atherosclerosis and the expansion of immunomodulatory agents that affect B-cell biology in clinical use and clinical trials for other disorders, it is important that the cardiovascular field be cognizant of potential beneficial or untoward effects of modulating B-cell activity on atherosclerosis.

Keywords: APRIL, A proliferation−inducing ligand; ApoE, apolipoprotein E; B-cell; BAFF, B-cell–activating factor; BAFFR, B-cell–activating factor receptor; BCMA, B-cell maturation antigen; BCR, B-cell receptor; Breg, regulatory B cell; CAD, coronary artery disease; CTLA4, cytotoxic T-lymphocyte–associated protein 4; CVD, cardiovascular disease; CXCR4, C-X-C motif chemokine receptor 4; GC, germinal center; GITR, glucocorticoid-induced tumor necrosis factor receptor–related protein; GITRL, glucocorticoid-induced tumor necrosis factor receptor–related protein ligand; GM-CSF, granulocyte-macrophage colony–stimulating factor; ICI, immune checkpoint inhibitor; IFN, interferon; IL, interleukin; IVUS, intravascular ultrasound; LDL, low-density lipoprotein; LDLR, low-density lipoprotein receptor; MDA-LDL, malondialdehyde-modified low-density lipoprotein; MI, myocardial infarction; OSE, oxidation-specific epitope; OxLDL, oxidized low-density lipoprotein; PC, phosphorylcholine; PD-1, programmed cell death protein 1; PD-L2, programmed death ligand 2; PDL1, programmed death ligand 1; RA, rheumatoid arthritis; SLE, systemic lupus erythematosus; TACI, transmembrane activator and CAML interactor; TNF, tumor necrosis factor; Treg, regulatory T cell; atherosclerosis; immunoglobulins; mAb, monoclonal antibody.

Publication types

  • Review