Heterogeneity of meningeal B cells reveals a lymphopoietic niche at the CNS borders

Author:

Brioschi Simone1ORCID,Wang Wei-Le1ORCID,Peng Vincent1ORCID,Wang Meng2ORCID,Shchukina Irina1,Greenberg Zev J.3ORCID,Bando Jennifer K.4ORCID,Jaeger Natalia1ORCID,Czepielewski Rafael S.1ORCID,Swain Amanda1ORCID,Mogilenko Denis A.1ORCID,Beatty Wandy L.5ORCID,Bayguinov Peter6,Fitzpatrick James A. J.678ORCID,Schuettpelz Laura G.3,Fronick Catrina C.9ORCID,Smirnov Igor1,Kipnis Jonathan1ORCID,Shapiro Virginia S.10ORCID,Wu Gregory F.11ORCID,Gilfillan Susan1ORCID,Cella Marina1ORCID,Artyomov Maxim N.1ORCID,Kleinstein Steven H.212ORCID,Colonna Marco1ORCID

Affiliation:

1. Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA.

2. Interdepartmental Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT 06511, USA.

3. Department of Pediatrics, Washington University School of Medicine, Saint Louis, MO 63110, USA.

4. Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.

5. Department of Molecular Microbiology, Center for Infectious Disease Research, Washington University School of Medicine, Saint Louis, MO 63110, USA.

6. Washington University Center for Cellular Imaging, Washington University School of Medicine, Saint Louis, MO 63110, USA.

7. Departments of Cell Biology and Physiology and Neuroscience, Washington University School of Medicine, Saint Louis, MO 63110, USA.

8. Department of Biomedical Engineering, Washington University in Saint Louis, Saint Louis, MO 63130, USA.

9. McDonnell Genome Institute, Washington University School of Medicine, Saint Louis, MO 63110, USA.

10. Department of Immunology, Mayo Clinic, Rochester, MN 55905, USA.

11. Department of Neurology, Washington University in Saint Louis, Saint Louis, MO 63110, USA.

12. Department of Pathology, Yale School of Medicine, New Haven, CT 06520, USA.

Abstract

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

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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