Age-associated B cells (ABCs) develop from a CNS-localized progenitor pool into a pro-inflammatory phenotype after stroke
Open accessAbstract
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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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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Cites
The single-cell transcriptional landscape of mammalian organogenesis
Cao, J., Spielmann, M., Qiu, X., Huang, X., Ibrahim, D. M., Hill, A. J., Zhang, F., Mundlos, S., Christiansen, L., Steemers, F. J., et al. (2019) · Nature · doi:10.1038/s41586-019-0969-x · Cited by 4,490 · see citing works
Förster, R., Schubel, A., Breitfeld, D., Kremmer, E., Renner‐Müller, I., Wolf, E., & Lipp, M. (1999) · Cell · doi:10.1016/s0092-8674(00)80059-8 · Cited by 2,348 · see citing works
B lymphocytes: how they develop and function
LeBien, T. W., & Tedder, T. F. (2008) · Blood · doi:10.1182/blood-2008-02-078071 · Cited by 1,400 · see citing works
Immune responses to stroke: mechanisms, modulation, and therapeutic potential.
Iadecola, C., Buckwalter, M. S., & Anrather, J. (2020) · Journal of Clinical Investigation · doi:10.1172/jci135530 · Cited by 853 · see citing works
hdWGCNA identifies co-expression networks in high-dimensional transcriptomics data
Morabito, S., Reese, F., Rahimzadeh, N., Miyoshi, E., & Swarup, V. (2023) · Cell Reports Methods · doi:10.1016/j.crmeth.2023.100498 · Cited by 773 · see citing works
Skull and vertebral bone marrow are myeloid cell reservoirs for the meninges and CNS parenchyma
Cugurra, A., Mamuladze, T., Rustenhoven, J., Dykstra, T., Beroshvili, G., Greenberg, Z. J., Baker, W., Papadopoulos, Z., Drieu, A., Blackburn, S., et al. (2021) · Science · doi:10.1126/science.abf7844 · Cited by 681 · see citing works
A B-cell subset uniquely responsive to innate stimuli accumulates in aged mice
Hao, Y., O'Neill, P., Naradikian, M. S., Scholz, J. L., & Cancro, M. P. (2011) · Blood · doi:10.1182/blood-2011-01-330530 · Cited by 622 · see citing works
Herisson, F., Frodermann, V., Courties, G., Rohde, D., Sun, Y., Vandoorne, K., Wojtkiewicz, G. R., Masson, G. S., Vinegoni, C., Kim, J., et al. (2018) · Nature Neuroscience · doi:10.1038/s41593-018-0213-2 · Cited by 610 · see citing works
Experimental Stroke Induces Massive, Rapid Activation of the Peripheral Immune System
Offner, H., Subramanian, S., Parker, S. M., Afentoulis, M. E., Vandenbark, A. A., & Hurn, P. D. (2005) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/sj.jcbfm.9600217 · Cited by 537 · see citing works
Heterogeneity of meningeal B cells reveals a lymphopoietic niche at the CNS borders
Brioschi, S., Wang, W.-L., Peng, V., Wang, M., Shchukina, I., Greenberg, Z. J., Bando, J. K., Jaeger, N., Czepielewski, R. S., Swain, A., et al. (2021) · Science · doi:10.1126/science.abf9277 · Cited by 472 · see citing works
Cancro, M. P. (2020) · Annual Review of Immunology · doi:10.1146/annurev-immunol-092419-031130 · Cited by 464 · see citing works
B-Lymphocyte-Mediated Delayed Cognitive Impairment following Stroke
Doyle, K. P., Quach, L. N., Solé, M., Axtell, R. C., Nguyen, T. V., Soler-Llavina, G. J., Jurado, S., Han, J., Steinman, L., Longo, F. M., et al. (2015) · Journal of Neuroscience · doi:10.1523/jneurosci.4098-14.2015 · Cited by 338 · see citing works
Regulatory B Cells Limit CNS Inflammation and Neurologic Deficits in Murine Experimental Stroke
Ren, X. S., Akiyoshi, K., Dziennis, S., Vandenbark, A. A., Herson, P. S., Hurn, P. D., & Offner, H. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.1623-11.2011 · Cited by 298 · see citing works
Unraveling B cell trajectories at single cell resolution
Morgan, D., & Tergaonkar, V. (2022) · Trends in Immunology · doi:10.1016/j.it.2022.01.003 · Cited by 232 · see citing works
Functional recovery after ischemic stroke—A matter of age
Knoflach, M., Matošević, B., Rücker, M., Furtner, M. T., Mair, A., Wille, G., Zangerle, A., Werner, P., Ferrari, J., Schmidauer, C., et al. (2012) · Neurology · doi:10.1212/wnl.0b013e31824367ab · Cited by 226 · see citing works
Transcriptional and epigenetic decoding of the microglial aging process
Li, X., Li, Y., Jin, Y., Zhang, Y., Wu, J., Xu, Z., Huang, Y., Cai, L., Gao, S., Liu, T., et al. (2023) · Nature Aging · doi:10.1038/s43587-023-00479-x · Cited by 225 · see citing works
Aging alters the immunological response to ischemic stroke
Ritzel, R. M., Lai, Y., Crapser, J. D., Patel, A. R., Schrecengost, A., Grenier, J. M., Mancini, N. S., Patrizz, A., Jellison, E. R., Morales‐Scheihing, D., et al. (2018) · Acta Neuropathologica · doi:10.1007/s00401-018-1859-2 · Cited by 209 · see citing works
Therapeutic B-cell depletion reverses progression of Alzheimer’s disease
Kim, K., Wang, X., Ragonnaud, E., Bodogai, M., Illouz, T., DeLuca, M., McDevitt, R. A., Gusev, F., Okun, E., Rogaev, E., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-22479-4 · Cited by 206 · see citing works
Schmitt, F. A., Nelson, P. T., Abner, E. L., Scheff, S. W., Jicha, G. A., Smith, C. D., Cooper, G. E., Mendiondo, M. S., Danner, D. D., Eldik, L. J. V., et al. (2012) · Current Alzheimer Research · doi:10.2174/156720512801322591 · Cited by 184 · see citing works
Self-citationVorontsov, I. E., Eliseeva, I. A., Zinkevich, A. O., Nikonov, M., Abramov, S., Boytsov, A., Kamenets, V., Kasianova, A. M., Kolmykov, S. K., Yevshin, I., et al. (2023) · Nucleic Acids Research · doi:10.1093/nar/gkad1077 · Cited by 163 · see citing works
Ortega, S. B., Torres, V. O., Latchney, S. E., Whoolery, C. W., Noorbhai, I., Poinsatte, K., Selvaraj, U. M., Benson, M. A., Meeuwissen, A., Plautz, E. J., et al. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1913292117 · Cited by 137 · see citing works
Self-citationMcCulloch, L. J., Smith, C. J., & McColl, B. W. (2017) · Nature Communications · doi:10.1038/ncomms15051 · Cited by 78 · see citing works
Stroke induces a rapid adaptive autoimmune response to novel neuronal antigens.
Ortega, S. B., Noorbhai, I., Poinsatte, K., Kong, X., Anderson, A. G., Monson, N. L., & Stowe, A. M. (2015) · PubMed · Cited by 76 · see citing works
Self-citationDoes B lymphocyte-mediated autoimmunity contribute to post-stroke dementia?
Doyle, K. P., & Buckwalter, M. S. (2016) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2016.08.009 · Cited by 71 · see citing works
Piovesan, D., Tempany, J. C., Pietro, A. D., Baas, I., Yiannis, C., O’Donnell, K., Chen, Y., Peperzak, V., Belz, G. T., Mackay, C. R., et al. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.03.060 · Cited by 65 · see citing works
High-throughput RNA sequencing of paraformaldehyde-fixed single cells
Phan, H. V., van Gent, M., Drayman, N., Basu, A., Gack, M. U., & Tay, S. (2021) · Nature Communications · doi:10.1038/s41467-021-25871-2 · Cited by 64 · see citing works
CD11b-mediated migratory property of peripheral blood B cells
Kawai, K., Tsuno, N. H., Matsuhashi, M., Kitayama, J., Osada, T., Yamada, J., Tsuchiya, T., Yoneyama, S., Watanabe, T., Takahashi, K., et al. (2005) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2005.03.021 · Cited by 63 · see citing works
CD4+ T cells promote delayed B cell responses in the ischemic brain after experimental stroke
Weitbrecht, L., Berchtold, D., Zhang, T., Jagdmann, S., Dames, C., Winek, K., Meisel, C., & Meisel, A. (2020) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2020.09.029 · Cited by 60 · see citing works
Evidence of Intrathecal Immunoglobulin Synthesis in Stroke
Prüß, H., Iggena, D., Baldinger, T., Prinz, V., Meisel, A., Endres, M., Dirnagl, U., & Schwab, J. M. (2012) · Archives of Neurology · doi:10.1001/archneurol.2011.3252 · Cited by 55 · see citing works
Antibodies to myelin basic protein are associated with cognitive decline after stroke
Becker, K. J., Tanzi, P. M., Zierath, D. K., & Buckwalter, M. S. (2016) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2016.04.001 · Cited by 55 · see citing works
Age-Associated B Cells in Autoimmune Diseases: Pathogenesis and Clinical Implications
Xie, G., Chen, X., Gao, Y., Yang, M., Zhou, S., Lu, L., Wu, H., & Lu, Q. (2025) · Clinical Reviews in Allergy & Immunology · doi:10.1007/s12016-025-09021-w · Cited by 54 · see citing works
Winkelmeier, L., Kniep, H. C., Faizy, T. D., Heitkamp, C., Holtz, L., Meyer, L., Flottmann, F., Heitkamp, A., Schell, M., Thomalla, G., et al. (2024) · JAMA Network Open · doi:10.1001/jamanetworkopen.2024.26007 · Cited by 54 · see citing works
Morris, G., Puri, B. K., OLIVE, L. S., Carvalho, A. F., Berk, M., & Maes, M. H. J. (2019) · Pharmacological Research · doi:10.1016/j.phrs.2019.104408 · Cited by 51 · see citing works
The immunopathology of B lymphocytes during stroke-induced injury and repair
Malone, M. K., Ujas, T. A., Britsch, D. R. S., Cotter, K. M., Poinsatte, K., & Stowe, A. M. (2022) · Seminars in Immunopathology · doi:10.1007/s00281-022-00971-3 · Cited by 44 · see citing works
Self-citationCD11bhigh B Cells Increase after Stroke and Regulate Microglia
Korf, J. M., Honarpisheh, P., Mohan, E. C., Banerjee, A., Blasco-Conesa, M. P., Honarpisheh, P., Guzman, G. U., Khan, R., Ganesh, B. P., Hazen, A. L., et al. (2022) · The Journal of Immunology · doi:10.4049/jimmunol.2100884 · Cited by 43 · see citing works
Hobson, R., Levy, S. H. S., Singal, C. M. S., Flaherty, D., Xiao, H., Ciener, B., Reddy, H., Zabinyakov, N., Kim, C. Y., Teich, A. F., et al. (2026) · Nature Immunology · doi:10.1038/s41590-025-02401-6 · Cited by 38 · see citing works
Human IgM–expressing memory B cells
Budeus, B., Kibler, A., & Küppers, R. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1308378 · Cited by 34 · see citing works
Wang, R., Li, H., Ling, C., Zhang, X., Lü, J., Luan, W., Zhang, J., & Shi, L. (2023) · Neural Regeneration Research · doi:10.4103/1673-5374.371365 · Cited by 33 · see citing works
The immunology of stroke and dementia
Iadecola, C., & Anrather, J. (2025) · Immunity · doi:10.1016/j.immuni.2024.12.008 · Cited by 32 · see citing works
The age-dependent immune response to ischemic stroke
Tuohy, M. C., Hillman, E. M. C., Marshall, R. S., & Agalliu, D. (2022) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2022.102670 · Cited by 23 · see citing works
Pélissier, A., Luo, S., Stratigopoulou, M., Guikema, J. E. J., & Martínez, M. R. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1123968 · Cited by 21 · see citing works
Relapse to cocaine seeking is regulated by medial habenula NR4A2/NURR1 in mice
Childs, J. E., Morabito, S., Das, S., Santelli, C., Pham, V., Kusche, K. M., Vera, V. A., Reese, F., Campbell, R. R., Matheos, D. P., et al. (2024) · Cell Reports · doi:10.1016/j.celrep.2024.113956 · Cited by 20 · see citing works
A monoclonal natural human IgM protects axons in the absence of remyelination
Wootla, B., Đenić, A., Warrington, A. E., & Rodriguez, M. (2016) · Journal of Neuroinflammation · doi:10.1186/s12974-016-0561-3 · Cited by 14 · see citing works
Torres, V. O., Turchan-Cholewo, J. T., Colson, M. K., Yanev, P. G., Britsch, D. R. S., Cotter, K. M., McAtee, A. M., Ujas, T. A., Mercurio, D., Kong, X., et al. (2025) · Neurobiology of Disease · doi:10.1016/j.nbd.2025.106819 · Cited by 8 · see citing works
Self-citationCelebrating 40 years of the University of Kentucky Alzheimer's Disease Research Center
Schmitt, F. A., Abner, E. L., Fardo, D. W., Gold, B. T., Jicha, G. A., Kryscio, R. J., Lee, D. C., Nelson, P. T., & Eldik, L. J. V. (2025) · Alzheimer s & Dementia · doi:10.1002/alz.70181 · Cited by 7 · see citing works
Self-citationFlorescu, A., Zuo, M., Wang, A. A., Champagne-Jorgensen, K. P., Noor, M. A., Ward, L. A., van Puijenbroek, E., Klein, C., & Gommerman, J. L. (2025) · The Journal of Experimental Medicine · doi:10.1084/jem.20241255 · Cited by 4 · see citing works
Oh, S.-G., Noh, J., Jang, E., & Youn, J. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1553089 · Cited by 3 · see citing works
Wu, Y., Li, C., Tang, J., Gao, X., Cheon, I. S., Zhu, B., Zhang, R., Fain, C. E., Hu, S. S., Narasimhan, H., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2025.12.15.694321
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Research works printed but not linked: 5
- [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
- [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
- [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
- [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
- [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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Is there a role for B cells in Alzheimer's disease?
Charavner, E.-L., Fillatreau, S., & El Behi, M. (2026) · Cellular Immunology · doi:10.1016/j.cellimm.2026.105154
- 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.
- ORCID
- Venue
- Journal of Neuroinflammation
- Publisher
- openRxiv
- Published
- 2026-03-04
- ISSN
- 1742-2094 (ISSN-L)
- PMC
- PMC12991099
- OpenAlex
- W7212298204
- Cited by
- 1
- References
- 48
- Citations by year
- 2026: 1
- FWCI
- 2.29
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- 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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