Cited by 642T-cell and B-cell ImmunologyImmune Response and InflammationLymphoma Diagnosis and Treatment

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A B-cell subset uniquely responsive to innate stimuli accumulates in aged mice

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Hao, Yi, O'Neill, Patrick, Naradikian, Martin S., Scholz, Jean L., Cancro, Michael P.·2011·Blood

DOI 10.1182/blood-2011-01-330530PMC PMC3152496

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Abstract

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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Authors: Hao, Y., O'Neill, P., Naradikian, M. S., Scholz, J. L., & Cancro, M. P.
Affiliations: University of Pennsylvania (US)
ORCID: Hao, Yi
Naradikian, Martin S.
Scholz, Jean L.
Cancro, Michael P.
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
DOI: 10.1182/blood-2011-01-330530
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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A B-cell subset uniquely responsive to innate stimuli accumulates in aged mice

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