Therapeutic Avenues to Modulate B-Cell Function in Patients With Cardiovascular Disease

Abstract

The adaptive immune system plays an important role in the development and progression of atherosclerotic cardiovascular disease. B cells can have both proatherogenic and atheroprotective roles, making treatments aimed at modulating B cells important therapeutic targets. The innate-like B-cell response is generally considered atheroprotective, while the adaptive response is associated with mixed consequences for atherosclerosis. Additionally, interactions of B cells with components of the adaptive and innate immune system, including T cells and complement, also represent key points for therapeutic regulation. In this review, we discuss therapeutic approaches based on B-cell depletion, modulation of B-cell survival, manipulation of both the antibody-dependent and antibody-independent B-cell response, and emerging immunization techniques.

Keywords: T-lymphocytes; atherosclerosis; cardiovascular diseases; cell survival; immunization.

Figure 1.

B-cell subset overview. Overview of B-cell developmental subsets and their generalized impact on atherosclerosis.^– CLP indicates common lymphoid progenitor; GM-CSF, granulocyte-macrophage colony-stimulating factor; IL, interleukin; and IRA, innate response activator.

Figure 2.

Avenues for B-cell modulation in cardiovascular disease. B cells have multiple therapeutic targets aimed at modulating their function; shown are B cell–related therapeutic targets and currently available drugs. APRIL indicates a proliferation-inducing ligand; BAFF, B-cell activating factor; BAFF-R, B-cell activating factor receptor; BCMA, B-cell maturation antigen; Breg, regulatory B cell; CD, cluster of differentiation; IL, interleukin; OxLDL, oxidized low-density lipoprotein; TACI, transmembrane activator and calcium-modulator and cyclophilin ligand interactor; and Tfh, T follicular helper cell.