PreprintCited by 1Neuroinflammation and Neurodegeneration MechanismsT-cell and B-cell ImmunologyMultiple Sclerosis Research Studies

Age-associated B cells (ABCs) develop from a CNS-localized progenitor pool into a pro-inflammatory phenotype after stroke

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McAtee, Annabel M., Kenwood, Mathew, Ujas, Thomas, Colson, Mary K., Watkins, Julie, Winford, Edric D., Cotter, Katherine M., Britsch, Daimen +13 more·2026·Journal of Neuroinflammation

Abstract

Aging and age-related diseases like ischemic stroke induce chronic lymphocyte recruitment into the central nervous system (CNS). Conflicting effects on post-stroke functional recovery, however, are secondary to the differences in responding lymphocyte populations that shift immunophenotype with both ischemic injury and age. To better define CNS-localized B cell subsets, we used flow cytometry, single-cell RNA sequencing, and B cell receptor sequencing on B cells isolated from uninjured and post-stroke brains of aged male and female mice. We identified a novel B1b cell progenitor pool distinct from canonical pleural and peritoneal B1 niches. Trajectory analysis showed B1b progenitors transition into age-associated B cell (ABC) subsets, and clonal expansion of IgM+ ABCs (ABC/B1b) and plasma cells following ischemic stroke. We also confirmed analogous ABCs and developing B cell populations in post-mortem human parenchymal tissue isolated from aged brain donors. These studies reveal unique B cell populations that proliferate within the aging CNS and are associated with impaired post-stroke functional recovery in mice. Identification of inflammatory, CNS-resident ABC/B1b cells that are conserved across species is critical as they have the potential to be sequestered from peripheral immunotherapies and/or contribute to age-related neurodegenerative diseases.

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Crossref · 10.64898/2026.03.02.709112

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  • ABC-like cells expressing CD11b and CD11c have been detected in AD postmortem brain tissue.

    “In addition, ABCslike cells expressing CD11b and CD11c have been detected in AD postmortem brain tissue [79].”

    From Is there a role for B cells in Alzheimer's disease? (2026) · cites this paper as [79]

    The Results section, “Identification of ABC populations in human post-mortem brains” (page unavailable), reports both CD11b+ and CD11c+ ABCs in postmortem brain samples. It separately reports CD11c+ ABC enrichment in an Alzheimer’s disease dataset, but does not establish that both marker-defined populations were detected specifically in AD postmortem brains. (LLM, conf=0.82)

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Research works printed but not linked: 5

  1. [31]Wang R.,, A novel phenotype of B cells associated with enhanced phagocytic capability and chemotactic function after ischemic stroke. Neural Regen Res, 2023. 18(11): p. 2413– 2423. 37282471 PMC10360087
  2. [38]Oh S.-G., Noh J., Jang E., and Youn J., The transcription repressor Bach2 is required for maintaining the B-1 cell population by regulating self-renewal. Frontiers in Immunology, 2025. Volume 16 - 2025. PMC11958198 40170867
  3. [44]Becker K.J., Tanzi P., Zierath D., and Buckwalter M.S., Antibodies to myelin basic protein are associated with cognitive decline after stroke. J Neuroimmunol, 2016. 295-296: p. 9– 11. 27235342 PMC4884610
  4. [49]Xie G.,, Age-Associated B Cells in Autoimmune Diseases: Pathogenesis and Clinical Implications. Clinical Reviews in Allergy & Immunology, 2025. 68(1): p. 18. 39960645 PMC11832777
  5. [52]Kawai K.,, CD11b-mediated migratory property of peripheral blood B cells. Journal of Allergy and Clinical Immunology, 2005. 116(1): p. 192– 197. 15990794

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Authors
McAtee, A. M., Kenwood, M., Ujas, T., Colson, M. K., Watkins, J., Winford, E. D., Cotter, K. M., Britsch, D., Betz, D., Turchan-Cholewo, J., Lutshumba, J., Stuart, C., Shah, G., Runice, L., Ebbert, M., Cherra, S., Nelson, P. T., Sturgill, J. L., Monson, N. L., Goldberg, M. P., & Stowe, A. M.
Affiliations
  • University of Kentucky (US)
  • Department of Neurology, Long School of Medicine, University of Texas at San Antonio, 7703 Floyd Curl Drive, MSC 7883, San Antonio, Texas 78229, USA
  • Columbia University Irving Medical Center (US)
  • The University of Texas at San Antonio Health Science Center (US)
  • The University of Texas Southwestern Medical Center (US)
Corresponding author
Stowe, Ann M.
Venue
Journal of Neuroinflammation
Publisher
openRxiv
Published
2026-03-04
ISSN
1742-2094 (ISSN-L)
OpenAlex
W7212298204
Cited by
1
References
48
Citations by year
2026: 1
FWCI
2.29
Type
journal article
Language
en
Open access
Locations
  • Journal of Neuroinflammation (publishedVersion, cc-by-nc-nd)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
  • National Institute of Neurological Disorders and Stroke (R01NS088555, RF1NS088555, F30NS141486, T32NS077889, R01NS129668, 3RF1NS088555-07A1S1)
  • National Institutes of Health (T32AG057461, P30 AG072946)
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
age-associated B cells, ischemic stroke, B cell progenitors, neuroinflammation, post-stroke functional recovery, plasma cells, clonal expansion, IgM+ B cells, B cell receptor repertoire, aging, neurodegenerative diseases, sex differences

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