B and T Cells Driving Multiple Sclerosis: Identity, Mechanisms and Potential Triggers

Historically, multiple sclerosis (MS) has been viewed as being primarily driven by T cells. However, the effective use of anti-CD20 treatment now also reveals an important role for B cells in MS patients. The results from this treatment put forward T-cell activation rather than antibody production b...

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Bibliographic Details
Published in:Frontiers in immunology 2020-05, Vol.11, p.760
Main Authors: van Langelaar, Jamie, Rijvers, Liza, Smolders, Joost, van Luijn, Marvin M
Format: Article
Language:English
Subjects:
Animals
B-Lymphocytes - immunology
CD8+ T cells
Central Nervous System - immunology
Cytokines - immunology
Epstein-Barr virus
genetic risk
Germinal Center - immunology
Humans
Immunology
Lymphocyte Activation
Mice
Multiple Sclerosis - immunology
Multiple Sclerosis - pathology
T-bet+ B cells
T-Lymphocytes - immunology
Th1/Th17
transmigration
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Summary:Historically, multiple sclerosis (MS) has been viewed as being primarily driven by T cells. However, the effective use of anti-CD20 treatment now also reveals an important role for B cells in MS patients. The results from this treatment put forward T-cell activation rather than antibody production by B cells as a driving force behind MS. The main question of how their interaction provokes both B and T cells to infiltrate the CNS and cause local pathology remains to be answered. In this review, we highlight key pathogenic events involving B and T cells that most likely contribute to the pathogenesis of MS. These include (1) peripheral escape of B cells from T cell-mediated control, (2) interaction of pathogenic B and T cells in secondary lymph nodes, and (3) reactivation of B and T cells accumulating in the CNS. We will focus on the functional programs of CNS-infiltrating lymphocyte subsets in MS patients and discuss how these are defined by mechanisms such as antigen presentation, co-stimulation and cytokine production in the periphery. Furthermore, the potential impact of genetic variants and viral triggers on candidate subsets will be debated in the context of MS.
ISSN:1664-3224
1664-3224
DOI:10.3389/fimmu.2020.00760