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Dual Role of B Cells in Multiple Sclerosis.

ABSTRACT: B cells have emerged as an important immune cell type that can be targeted for therapy in multiple sclerosis (MS). Depleting B cells with anti-CD20 antibodies is effective in treating MS. Yet, atacicept treatment, which blocks B-cell Activating Factor (BAFF) and A Proliferation-Inducing Ligand (APRIL), two cytokines important for B cell development and function, paradoxically increases disease activity in MS patients. The reason behind the failure of atacicept is not well understood. The stark differences in clinical outcomes with these therapies demonstrate that B cells have both inflammatory and anti-inflammatory functions in MS. In this review, we summarize the importance of B cells in MS and discuss the different B cell subsets that perform inflammatory and anti-inflammatory functions and how therapies modulate B cell functions in MS patients. Additionally, we discuss the potential anti-inflammatory functions of BAFF and APRIL on MS disease.

SUBMITTER: Kumar G

PROVIDER: S-EPMC9916779 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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Dual Role of B Cells in Multiple Sclerosis.

Kumar Gaurav G Axtell Robert C RC

International journal of molecular sciences 20230125 3

B cells have emerged as an important immune cell type that can be targeted for therapy in multiple sclerosis (MS). Depleting B cells with anti-CD20 antibodies is effective in treating MS. Yet, atacicept treatment, which blocks B-cell Activating Factor (BAFF) and A Proliferation-Inducing Ligand (APRIL), two cytokines important for B cell development and function, paradoxically increases disease activity in MS patients. The reason behind the failure of atacicept is not well understood. The stark d ...[more]

PMID: 36768658

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Project description:Introduction Multiple sclerosis is an inflammatory and demyelinating disease caused by a pathogenic immune response against the myelin sheath surfaces of oligodendrocytes. The demyelination has been classically associated with pathogenic B cells residing in the central nervous system that release autoreactive antibodies against myelin. The aim of the present study was to investigate whether extracellular vesicles (EVs) mediate delivery of myelin autoreactive antibodies from peripheral B cells against oligodendrocytes in multiple sclerosis (MS) and to analyze whether these EVs could mediate demyelination in vitro. We also studied the role of these EV-derived myelin antibodies as a diagnostic biomarker in MS. Methods This is a prospective, observational, and single-center study that includes patients with MS and two control groups: patients with non-immune white matter lesions and healthy controls. We isolated B-cell-derived EVs from the blood and cerebrospinal fluid (CSF) and analyzed their myelin antibody content. We also studied whether antibody-loaded EVs reach oligodendrocytes in patients with MS and the effect on demyelination of B-cell-derived EVs containing antibodies in vitro. Results This study enrolled 136 MS patients, 23 white matter lesions controls, and 39 healthy controls. We found autoreactive myelin antibodies in EVs that were released by peripheral B cells, but not by populations of B cells resident in CSF. We also identified a cut-off of 3.95 ng/mL of myelin basic protein autoantibodies in EVs from peripheral B cells, with 95.2% sensitivity and 88.2% specificity, which allows us to differentiate MS patients from healthy controls. EV-derived myelin antibodies were also detected in the oligodendrocytes of MS patients. Myelin antibody-loaded EVs from B cells induced myelin markers decrease of oligodendrocytes in vitro. Discussion Peripheral reactive immune cells could contribute remotely to MS pathogenesis by delivering myelin antibodies to oligodendrocytes. EV-derived myelin antibodies could play a role as diagnostic biomarker in MS.

Dataset Information

Dual Role of B Cells in Multiple Sclerosis.

Publications

Dual Role of B Cells in Multiple Sclerosis.

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