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B cells in central nervous system disease: diversity, locations and pathophysiology

Nature Reviews Immunology volume 22, pages 513–524 (2022)Cite this article

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Abstract

B cells represent a relatively minor cell population within both the healthy and diseased central nervous system (CNS), yet they can have profound effects. This is emphasized in multiple sclerosis, in which B cell-depleting therapies are arguably the most efficacious treatment for the condition. In this Review, we discuss how B cells enter and persist in the CNS and how, in many neurological conditions, B cells concentrate within CNS barriers but are rarely found in the parenchyma. We highlight how B cells can contribute to CNS pathology through antibody secretion, antigen presentation and secretion of neurotoxic molecules, using examples from CNS tumours, CNS infections and autoimmune conditions such as neuromyelitis optica and, in particular, multiple sclerosis. Overall, understanding common and divergent principles of B cell accumulation and their effects within the CNS could offer new insights into treating these devastating neurological conditions.

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Fig. 1: T cell-dependent B cell differentiation.
Fig. 2: Locations of B cells in multiple sclerosis lesions.
Fig. 3: Mechanisms of B cell recruitment into the CNS.
Fig. 4: Direct and indirect mechanisms that B cells use to affect multiple sclerosis pathology.

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Acknowledgements

R.W.J. acknowledges postdoctoral fellowship funding from the University of Calgary Eyes High program, the Multiple Sclerosis of Canada and Roche unrestricted educational fellowship. V.W.Y. acknowledges salary support from the Canada Research Chair Tier 1 program and operating grant support from the Canadian Institutes of Health Research and the Multiple Sclerosis Society of Canada.

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  1. Hotchkiss Brain Institute and the Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada

    Rajiv W. Jain & V. Wee Yong

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  1. Rajiv W. Jain
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Correspondence to V. Wee Yong.

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Glossary

B1 B cells

A subset of mature B cells with limited B cell receptor diversity predominantly found within the peritoneal and pleural cavities that typically differentiates directly into plasma cells, forming few memory cells.

Follicular B cells

A subset of mature B cells, also known as B2 B cells, that represents the majority of B cells in the body and are commonly found within all lymphoid organs.

Marginal zone B cells

A subset of mature B cells with limited B cell receptor diversity that is predominantly found in the marginal zone of the spleen and which typically differentiates directly into plasma cells but can also generate memory cells.

Germinal centre B cells

This subset of activated B cells is an intermediate stage of differentiation and is the precursor of higher-affinity memory B cells and plasma cells.

Memory B cells

A subset of B cells that is antigen experienced and has reacquired a quiescent phenotype and can participate in secondary immune responses, or sometimes refers to activated B cells that retain an activated phenotype.

T-bet+ memory B cells

A subset of memory B cells that expresses the transcription factor T-bet whose numbers tend to increase with age as well as in autoimmune disorders and viral infections.

Plasma cells

Terminally differentiated B cells that produce large amounts of antibodies and are short-lived unless they find a survival niche allowing long-term maintenance.

Regulatory B (Breg) cells

This subset of B cells suppresses inflammation through the secretion of anti-inflammatory proteins or through physical interactions.

Plasmablasts

The precursor to plasma cells that has begun to produce antibodies but also retains some features of B cells, such as surface B cell receptor and MHC class II expression, and is still proliferating.

T helper 17 (TH17) cells

A subset of CD4+ T cells characterized by the expression of the transcription factor RORγT and the expression of IL-17A that is commonly associated with immunity against extracellular pathogens.

T follicular helper cells

A subset of CD4+ T cells characterized by the expression of the transcriptional repressor Bcl6 and the chemokine receptor CXCR5 allowing these cells to co-localize with B cells and promote their differentiation through physical interactions.

T helper 1 (TH1) cells

A subset of CD4+ T cells characterized by the expression of the transcription factor T-bet and the expression of IFNγ that is commonly associated with cellular immunity.

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Jain, R.W., Yong, V.W. B cells in central nervous system disease: diversity, locations and pathophysiology. Nat Rev Immunol 22, 513–524 (2022). https://doi.org/10.1038/s41577-021-00652-6

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