Heterogeneity of meningeal B cells reveals a lymphopoietic niche at the CNS borders
Open accessAbstract
Getting around the blood–brain barrier: The meninges comprise three membranes that surround and protect the central nervous system (CNS). Recent studies have noted the existence of myeloid cells resident there, but little is known about their ontogeny and function, and whether other meningeal immune cell populations have important roles remains unclear (see the Perspective by Nguyen and Kubes). Cugurra et al. found in mice that a large proportion of continuously replenished myeloid cells in the dura mater are not blood derived, but rather transit from cranial bone marrow through specialized channels. In models of CNS injury and neuroinflammation, the authors demonstrated that these myeloid cells have an immunoregulatory phenotype compared with their more inflammatory blood-derived counterparts. Similarly, Brioschi et al. show that the meninges host B cells that are also derived from skull bone marrow, mature locally, and likely acquire a tolerogenic phenotype. They further found that the brains of aging mice are infiltrated by a second population of age-associated B cells, which come from the periphery and may differentiate into autoantibody-secreting plasma cells after encountering CNS antigens. Together, these two studies may inform future treatment of neurological diseases. Science , abf7844, abf9277, this issue p. eabf7844 , p. eabf9277 ; see also abj8183, p. 396
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Meningeal B cells are uniquely positioned to interact with CNS-specific antigens, including those linked to Aβ plaques and tau pathology in AD.
“These data suggest that meningeal B cells are uniquely positioned to interact with CNS-specific antigens, including those linked to A β plaques and tau pathology in AD.”
From Is there a role for B cells in Alzheimer's disease? (2026) · cites this paper as [105]
The Discussion (page unavailable) reports that meningeal B cells have functional receptors that engage self-antigens and suggests local selection against cells reactive to CNS epitopes. This supports the general possibility of interaction with CNS antigens, but the paper does not connect those interactions to Aβ plaques, tau pathology, or Alzheimer’s disease. (LLM, conf=0.86)
Experimental — accuracy not yet measuredThe skull bone marrow serves as a local, CNS-specific reservoir of B cells, encompassing a broad spectrum of developmental stages from pro-B to mature B cells.
“the skull bone marrow serves as a local, CNS-specific reservoir of B cells, encompassing a broad spectrum of developmental stages from pro-B to mature B cells [105].”
From Is there a role for B cells in Alzheimer's disease? (2026) · cites this paper as [105]
These B cells populate the meninges, where they migrate via specialized vascular channels that circumvent systemic circulation.
“These B cells populate the meninges, a protective triple-layered membrane system surrounding the CNS where they migrate via specialized vascular channels that circum vent systemic circulation [105,106].”
From Is there a role for B cells in Alzheimer's disease? (2026) · cites this paper as [105]
During aging, the meninges undergo a shift towards pro-inflammatory immune responses, characterized by an increased number of T cells and B cells.
“During aging, the meninges undergo a shift towards pro-inflammatory immune responses, characterized by an increased number of T cells and B cells.”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [682]
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- Authors
- Brioschi, S., Wang, W.-L., Peng, V., Wang, M., Shchukina, I., Greenberg, Z. J., Bando, J. K., Jaeger, N., Czepielewski, R. S., Swain, A., Mogilenko, D. A., Beatty, W. L., Bayguinov, P., Fitzpatrick, J. A. J., Schuettpelz, L. G., Fronick, C. C., Smirnov, I., Kipnis, J., Shapiro, V. S., Wu, G. F., Gilfillan, S., Cella, M., Artyomov, M. N., Kleinstein, S. H., & Colonna, M.
- Affiliations
- Washington University in St. Louis (US)
- Yale University (US)
- Stanford Medicine (US)
- Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA.
- Mayo Clinic (US)
- Corresponding author
- Colonna, Marco
- ORCID
- Brioschi, Simone
- Wang, Wei-Le
- Peng, Vincent
- Wang, Meng
- Greenberg, Zev J.
- Bando, Jennifer K.
- Jaeger, Natalia
- Czepielewski, Rafael S.
- Swain, Amanda
- Mogilenko, Denis A.
- Beatty, Wandy L.
- Bayguinov, Peter
- Fitzpatrick, James A. J.
- Schuettpelz, Laura G.
- Fronick, Catrina C.
- Smirnov, Igor
- Kipnis, Jonathan
- Shapiro, Virginia S.
- Wu, Gregory F.
- Gilfillan, Susan
- Cella, Marina
- Artyomov, Maxim N.
- Kleinstein, Steven H.
- Colonna, Marco
- Venue
- Science
- Published
- 2021-07-23
- Volume
- 373
- Issue
- 6553
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC8448524
- OpenAlex
- W3165520347
- Cited by
- 472
- References
- 51
- Citations by year
- 2026: 87 · 2025: 87 · 2024: 79 · 2023: 88 · 2022: 101 · 2021: 29
- FWCI
- 29.75
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (RF1AG051485, RF1AG059082)
- National Institute of Allergy and Infectious Diseases (R01AI104739)
- National Institute of Diabetes and Digestive and Kidney Diseases (F30DK127540, K99DK118110, T32DK077653)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (P30AR073752)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Keywords
- dura mater, blood-brain barrier, central nervous system injury, neuroinflammation, age-associated B cells
- MeSH terms
- Immune Privilege, Aging, Animals, B-Lymphocytes, Bone Marrow Cells, Cell Movement, Central Nervous System, Dura Mater, Fibroblasts, Homeostasis, Meninges, Plasma Cells, Skull, B-Lymphocyte Subsets, Lymphopoiesis, Mice, Single-Cell Analysis
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