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.
Highlights
These new-generation medicines have helped improve the quality of life and extend the life expectancy of patients; Multiple sclerosis (MS) still is uncurable and forms a substantial burden on patients, families, and the health care system [2]
This review focuses on the role of a unique B-cell subtype that participates in innate immunity, contributes to autoimmunity, and is presumably involved in MS
B1 cell” (B1 cell) might identify their specific antigens within the central nervous system (CNS) and migrate back and forth to the regional lymph nodes through the neuro–lymphatic system (Figure 3)
Summary
Multiple sclerosis (MS) is a chronic neuro–immunological demyelinating disease of the central nervous system (CNS) characterized by prototypic multifocal neurodegeneration of white and gray matter [1]. A large arsenal of new therapeutics has been developed in recent years that delay MS progression and reduce the chance of disability [5,6]. These new-generation medicines have helped improve the quality of life and extend the life expectancy of patients; MS still is uncurable and forms a substantial burden on patients, families, and the health care system [2]. B cells participate in different stages of MS; they take part in antigen presentation to self-reactive T cells. Thereby they might trigger an (unsought) immune response and can secrete pro- and anti-inflammatory cytokines (a group of immunomodulatory signaling proteins) [15–17]. As B1 cells’ functional importance is just starting to unravel, this review’s primary goal is two-fold: (1) to provide an up-to-date overview of the human B1 cell’s physiological role in health and (2) to discuss evidence for its role in MS and the consequence of its dysregulated physiology
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