The Forgotten Brother: The Innate-like B1 Cell in Multiple Sclerosis

Abstract

Multiple sclerosis (MS) is a neurodegenerative disease of the central nervous system (CNS), traditionally considered a chronic autoimmune attack against the insulating myelin sheaths around axons. However, the exact etiology has not been identified and is likely multi-factorial. Recently, evidence has been accumulating that implies that autoimmune processes underlying MS may, in fact, be triggered by pathological processes initiated within the CNS. This review focuses on a relatively unexplored immune cell—the “innate-like” B1 lymphocyte. The B1 cell is a primary-natural-antibody- and anti-inflammatory-cytokine-producing cell present in the healthy brain. It has been recently shown that its frequency and function may differ between MS patients and healthy controls, but its exact involvement in the MS pathogenic process remains obscure. In this review, we propose that this enigmatic cell may play a more prominent role in MS pathology than ever imagined. We aim to shed light on the human B1 cell in health and disease, and how dysregulation in its delicate homeostatic role could impact MS. Furthermore, novel therapeutic avenues to restore B1 cells’ beneficial functions will be proposed.

The role of B-1 cells in cancer progression and anti-tumor immunity

“…Some of the functions of B-1 cells have made them a focus of research in the field of autoimmunity. Mounting evidence suggests that B-1 cells are involved in the development of autoimmune diseases such as multiple sclerosis (MS) ( 61 ) and systemic lupus erythematosus (SLE) ( 62 ).…”

B Cells Dynamic in Aging and the Implications of Nutritional Regulation

“…Research indicates that B-1 cells, producing IgM early in ontogeny, play a regulatory role in the development of both B-1 and B-2 cells [ 4 ]. The impact of B-1 cell antibodies extends to various diseases [ 5 , 6 , 7 ], as evidenced by a diminished B-1 cell frequency observed in individuals with relapsing-remitting multiple sclerosis when compared to those without such conditions [ 8 ]. Mature B-2 cells rely on the B-cell activating factor (BAFF)–B-cell activating factor receptor (BAFFR) signaling pathway for development and survival [ 9 ].…”

B-1 cells in immunotoxicology: Mechanisms underlying their response to chemicals and particles

“…However, it has been established that the pool of B-1 cells adapts to the pathogen under inflammatory conditions ( Patel and Kearney, 2015 ; New et al, 2020 ). Thus, whether studied at a given time or over a lifetime, the B-1 cell subset contains cells with variations in their functions/specificities, as explained below and in Figure 2 ( Halperin et al, 2022 ).…”

“…B-1 cells can be seen as pleiotropic multifaceted precursors or as a collection of several subsets of fully differentiated cells ( Popi et al, 2012 ), including adaptive immune cells ( Cole et al, 2009 ; Smith and Baumgarth, 2019 ). The new understanding that B-1 cells comprise a variety of subsets explains the exponentially growing interest toward these cells in applied immunology and toxicology ( Haro et al, 2019 ; Aziz et al, 2020 ; Halperin et al, 2022 ; She et al, 2022 ).…”