B Cell Subsets and Atherosclerosis: Updates and Emerging Concepts

Immunological Reviews, vol. 339, pp. e70124

Abstract

ABSTRACT Atherosclerotic cardiovascular disease (ASCVD) is increasingly recognized not just as a lipid‐driven disease, but as a complex interplay between vascular cells and the immune system. Accumulating evidence highlights a central, yet heterogeneous role for B cells in atherogenesis, with distinct subsets displaying opposing roles. In this review, we provide an in‐depth overview of the contributions of B cell subsets to ASCVD, including emerging insights into the roles and pathways of atheroprotective innate B cells producing IgM against oxidation‐specific epitopes (IgM OSE ) and newly appreciated age‐associated B cells (ABCs), a distinct subset that accumulates with aging and potentially exacerbates atherosclerosis. By integrating insights from preclinical models and human studies, we describe the mechanisms through which B cell subsets influence ASCVD, including antigen presentation and immune checkpoint‐mediated communication, secretion of cytokines and chemokines, and we highlight that humoral immunity in atherosclerosis reflects a context‐dependent interplay between antibody effector properties and antigenic targets rather than antibody class alone. Finally, we explore how the advances in our understanding of B cells may guide the development of more targeted immunomodulatory therapies that enhance atheroprotective B cell functions while limiting atherogenic responses.

Authors 4

1. Sophieke Lems Aachen Division of BioTherapeutics

   Leiden University

   Affiliation as printed

   Division of BioTherapeutics, Leiden Academic Centre for Drug Research Leiden University Leiden the Netherlands

2. Megan Mazzei

   University of Virginia

   Affiliation as printed

   Beirne B. Carter Center for Immunology Research University of Virginia Charlottesville Virginia USA

3. Amanda C. Foks corresponding Aachen Division of BioTherapeutics

   Leiden University

   Affiliation as printed

   Division of BioTherapeutics, Leiden Academic Centre for Drug Research Leiden University Leiden the Netherlands

4. Coleen A. McNamara corresponding

   University of Virginia

   Affiliation as printed

   Beirne B. Carter Center for Immunology Research University of Virginia Charlottesville Virginia USA

   Division of Cardiovascular Medicine, Department of Medicine University of Virginia Charlottesville Virginia USA