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Review
. 2022 Jun 7;12(6):800.
doi: 10.3390/biom12060800.

Breaching Brain Barriers: B Cell Migration in Multiple Sclerosis

Carla Rodriguez-Mogeda  1 , Sabela Rodríguez-Lorenzo  1 , Jiji Attia  1 , Jack van Horssen  1 , Maarten E Witte  1 , Helga E de Vries  1
Affiliations
Review

Breaching Brain Barriers: B Cell Migration in Multiple Sclerosis

Carla Rodriguez-Mogeda et al. Biomolecules. .

Abstract

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS) known for the manifestation of demyelinated lesions throughout the CNS, leading to neurodegeneration. To date, not all pathological mechanisms that drive disease progression are known, but the clinical benefits of anti-CD20 therapies have put B cells in the spotlight of MS research. Besides their pathological effects in the periphery in MS, B cells gain access to the CNS where they can contribute to disease pathogenesis. Specifically, B cells accumulate in perivascular infiltrates in the brain parenchyma and the subarachnoid spaces of the meninges, but are virtually absent from the choroid plexus. Hence, the possible migration of B cells over the blood-brain-, blood-meningeal-, and blood-cerebrospinal fluid (CSF) barriers appears to be a crucial step to understanding B cell-mediated pathology. To gain more insight into the molecular mechanisms that regulate B cell trafficking into the brain, we here provide a comprehensive overview of the different CNS barriers in health and in MS and how they translate into different routes for B cell migration. In addition, we review the mechanisms of action of diverse therapies that deplete peripheral B cells and/or block B cell migration into the CNS. Importantly, this review shows that studying the different routes of how B cells enter the inflamed CNS should be the next step to understanding this disease.

Keywords: B cells; blood–CSF barrier; blood–brain barrier; blood–meningeal barrier; multiple sclerosis.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Schematic representation of the different CNS barriers and their localization in health. (a) Blood–brain barrier; (b) blood–CSF barrier in the choroid plexus; and (c) blood–meningeal barrier. CSF, cerebrospinal fluid.
Figure 2
Figure 2
B cell development and differentiation.
Figure 3
Figure 3
Schematic representation of B cell migration across the different CNS barriers in multiple sclerosis.
See this image and copyright information in PMC

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Publication types

Grants and funding

This research was funded by the Dutch MS Research Foundation (MS18-358) to H.E.d.V. and (MS20-1106) to M.E.W.