Functional Role of B Cells in Atherosclerosis

Abstract

Atherosclerosis is a lipid-driven inflammatory disease of blood vessels, and both innate and adaptive immune responses are involved in its development. The impact of B cells on atherosclerosis has been demonstrated in numerous studies and B cells have been found in close proximity to atherosclerotic plaques in humans and mice. B cells exert both atheroprotective and pro-atherogenic functions, which have been associated with their B cell subset attribution. While B1 cells and marginal zone B cells are considered to protect against atherosclerosis, follicular B cells and innate response activator B cells have been shown to promote atherosclerosis. In this review, we shed light on the role of B cells from a different, functional perspective and focus on the three major B cell functions: antibody production, antigen presentation/T cell interaction, and the release of cytokines. All of these functions have the potential to affect atherosclerosis by multiple ways and are dependent on the cellular milieu and the activation status of the B cell. Moreover, we discuss B cell receptor signaling and the mechanism of B cell activation under atherosclerosis-prone conditions. By summarizing current knowledge of B cells in and beyond atherosclerosis, we are pointing out open questions and enabling new perspectives.

Investigation of Lymphocyte Subsets in Peripheral Blood of Patients with Dyslipidemia

“…B cells have three main effects: the production of antibody, the presentation of antigen or T cell interaction, and the release of cell factor. It was reported that all of the effect can regulate atherosclerosis and were associated with the activation status of the B cells, 17 which was consistent with the enhanced expression of B cells in patients with dyslipidemia observed in our experiment. Other experimental data indicated that changes in cellular lipid metabolism may have critical effects on humoral and cellular immunity, especially T cells and T cell subsets proliferation and cell fate decisions.…”

GPR55 in B cells limits atherosclerosis development and regulates plasma cell maturation

“…It is well described that an imbalance of B cell homeostasis can cause devastating effects and tissue injury. 10,13,33,34 The hyperactivated and dysfunctional B cell state together with an exaggerated antibody production in hypercholesterolemic mice lacking functional GPR55 signaling fits well to the proatherogenic phenotype. [35][36][37][38] B cell maturation and activation is precisely controlled by multiple factors, but begins with the binding of B-cell receptor (BCR) to a specific antigen, 39 such as an OSE.…”

“…10 Under hypercholesterolemic conditions, B cells may become hyperactivated with deregulation of plasma cell formation, thereby promoting atherosclerosis. 10,13 GPR55 is a G protein-coupled orphan receptor expressed by various leukocyte subsets, including B and T cells, but also natural killer cells, monocytes, macrophages, and neutrophils. According to murine immune cell transcriptomic data (Immgen.org), 14 GPR55 is highly expressed by splenic plasma cells (PC) and, to a lower extent, MZ B cells.…”

Immunity in Atherosclerosis: Focusing on T and B Cells

“…It has also recently been reported that MZB cells have thermal protective activity. Using a genetic model of MZB cell deficiency, it has been shown that the role of MZB in the negative regulation of proatherogenic TFH cells, via the PDL1 (programmed cell death ligand 1) axis, programmes cell death 1 [89]. Before this, it was assumed that a potential atheroprotective role might appear through the secretion of OSE-specific antibodies.…”