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A B-cell subset uniquely responsive to innate stimuli accumulates in aged mice
Open accessAbstract
We have discovered a distinct mature B-cell subset that accumulates with age, which we have termed age-associated B cells. These cells comprise up to 30% of mature B cells by 22 months. Despite sharing some features with other mature B-cell subsets, they are refractory to BCR and CD40 stimulation. Instead, they respond to TLR9 or TLR7 stimulation and divide maximally on combined BCR and TLR ligation, leading to Ig production and preferential secretion of IL-10 and IL-4. Although similar to follicular B cells in both B-lymphocyte stimulator (BLyS) receptor expression and BLyS binding capacity, these cells do not rely on BLyS for survival. They are neither cycling nor the result of intrinsically altered B lymphopoiesis in aged BM, but instead appear to be generated from mature B cells that exhaustively expand during the individual's lifetime. Finally, they present Ag effectively and favor polarization to a TH17 profile. Together, these findings reveal that while the magnitude of the mature primary B-cell niche is maintained with age, it is increasingly occupied by cells refractory to BCR-driven activation yet responsive to innate receptor stimulation.
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“Age-associated B cells (ABCs) are an heterogeneous subset of mature B lymphocytes that accumulate progressively with advancing age and can represent up to 30% of splenic mature B cells in very old mice [69].”
From Is there a role for B cells in Alzheimer's disease? (2026) · cites this paper as [69]
In the citing paper
“They are charac terized in mice by the surface phenotype CD19 + , CD11c + , T-bet + , CD11b + , CD21 , CD23 , CD86 + , MHCII + , and in humans by CD11c + , Tbet + , CD27 , IgD , CD38 , CD21 [69 -72].”
From Is there a role for B cells in Alzheimer's disease? (2026) · cites this paper as [69]
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Day, C. L., Kaufmann, D. E., Kiepiela, P., Brown, J. A., Moodley, E. S., Reddy, S., Mackey, E. W., Miller, J. D., Leslie, A. J., DePierres, C., et al. (2006) · Nature · doi:10.1038/nature05115 · Cited by 2,680
Blackburn, S. D., Shin, H., Haining, W. N., Zou, T., Workman, C. J., Polley, A., Betts, M. R., Freeman, G. J., Vignali, D. A. A., & Wherry, E. J. (2009) · Nature Immunology · doi:10.1038/ni.1679 · Cited by 2,062
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Leadbetter, E. A., Rifkin, I. R., Hohlbaum, A. M., Beaudette-Zlatanova, B. C., Shlomchik, M. J., & Marshak‐Rothstein, A. (2002) · Nature · doi:10.1038/416603a · Cited by 1,929
Wherry, E. J., Blattman, J. N., Murali‐Krishna, K., der Most, R. G. V., & Ahmed, R. (2003) · Journal of Virology · doi:10.1128/jvi.77.8.4911-4927.2003 · Cited by 1,645
Moir, S. L., Ho, J., Malaspina, A., Wang, W., DiPoto, A. C., O’Shea, M. A., Roby, G. A., Kottilil, S., Arthos, J. A., Proschan, M. A., et al. (2008) · The Journal of Experimental Medicine · doi:10.1084/jem.20072683 · Cited by 894
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Metadata
- Authors
- Hao, Y., O'Neill, P., Naradikian, M. S., Scholz, J. L., & Cancro, M. P.
- Affiliations
- University of Pennsylvania (US)
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2011-08-04
- Volume
- 118
- Issue
- 5
- Pages
- 1294-1304
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- PMC
- PMC3152496
- OpenAlex
- W2071368241
- Cited by
- 622
- References
- 51
- Citations by year
- 2026: 62 · 2025: 78 · 2024: 65 · 2023: 65 · 2022: 63 · 2021: 84 · 2020: 45 · 2019: 35 · 2018: 26 · 2017: 30 · 2016: 13 · 2015: 11 · 2014: 16 · 2013: 13 · 2012: 12
- FWCI
- 6.39
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Blood (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (R01AG030227, AG030227)
- National Institute of Allergy and Infectious Diseases (R01AI073939, AI073939, T32AI055428)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Health Sciences › Medicine › Pathology and Forensic Medicine › Lymphoma Diagnosis and Treatment
- Keywords
- age-associated B cells, B cell aging, innate immune activation, TLR9, TLR7, B cell receptor signaling, CD40, B lymphocyte stimulator, follicular B cells, IL-10, IL-4, antigen presentation, Th17 polarization, B cell exhaustion, immunosenescence
- MeSH terms
- Aging, Animals, Cells, Cultured, Female, Immunity, Innate, Lymphocyte Activation, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Inbred DBA, Mice, Transgenic, B-Lymphocyte Subsets, Lymphocyte Count, Cell Proliferation, Mice, B-Cell Activating Factor
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