Age-Associated B Cells

Cancro, Michael P.

doi:10.1146/annurev-immunol-092419-031130

Cited by 464T-cell and B-cell ImmunologyImmune Response and InflammationImmune responses and vaccinations

Age-Associated B Cells

Cancro, Michael P.·2020·Annual Review of Immunology

DOI 10.1146/annurev-immunol-092419-031130

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Abstract

The age-associated B cell subset has been the focus of increasing interest over the last decade. These cells have a unique cell surface phenotype and transcriptional signature, and they rely on TLR7 or TLR9 signals in the context of Th1 cytokines for their formation and activation. Most are antigen-experienced memory B cells that arise during responses to microbial infections and are key to pathogen clearance and control. Their increasing prevalence with age contributes to several well-established features of immunosenescence, including reduced B cell genesis and damped immune responses. In addition, they are elevated in autoimmune and autoinflammatory diseases, and in these settings they are enriched for characteristic autoantibody specificities. Together, these features identify age-associated B cells as a subset with pivotal roles in immunological health, disease, and aging. Accordingly, a detailed understanding of their origins, functions, and physiology should make them tractable translational targets in each of these settings.

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ABC differentiation is driven by a combination of BCR ligation, TLR7 and 9 engagement, cytokine exposure to IFNγ and IL-21, and can occur independently of germinal center reactions via a T-independent extrafollicular pathway.
“Their differentiation is driven by a combination of BCR ligation, toll-like re ceptor (TLR) 7 and 9 engagement, cytokine exposure to IFNγ and IL-21, and can occur independently of germinal center reactions via a T-in dependent extrafollicular pathway [76].”
From Is there a role for B cells in Alzheimer's disease? (2026) · cites this paper as [76]
In addition to ageing, ABCs expand prematurely in the context of chronic immune activation, including autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis, Sjögren's syndrome, and multiple sclerosis.
“In addition to ageing, ABCs expand prematurely in the context of chronic immune activation, including autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis, Sj ¨ ogren's syndrome, and multiple sclerosis [76].”
From Is there a role for B cells in Alzheimer's disease? (2026) · cites this paper as [76]
Human age-associated B cells have been implicated in autoimmune disease, chronic viral infections, and COVID-19.
“In humans, these cells are found within the late memory fraction (IgD-CD27-, also called double negative B cells), secrete inflammatory mediators like TNFα, IL-6, IL-8, and have been implicated in autoimmune disease, chronic viral infections, and more recently in COVID-19156-158.”
From SARS-CoV-2, COVID-19 and the aging immune system (2021) · cites this paper as [156]
In mice, age-associated B cells are promoted by TLR7 responses.
“In mice, these cells are promoted by TLR7 responses156, which is relevant being a major PRR for SARS-CoV-2.”
From SARS-CoV-2, COVID-19 and the aging immune system (2021) · cites this paper as [156]
In humans, age-associated B cells are found within the late memory fraction (IgD-CD27-, also called double negative B cells).
“In humans, these cells are found within the late memory fraction (IgD-CD27-, also called double negative B cells), secrete inflammatory mediators like TNFα, IL-6, IL-8, and have been implicated in autoimmune disease, chronic viral infections, and more recently in COVID-19156-158.”
From SARS-CoV-2, COVID-19 and the aging immune system (2021) · cites this paper as [156]

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Authors: Cancro, M. P.
Affiliations: University of Pennsylvania (US)
Corresponding author: Cancro, Michael P.
ORCID: Cancro, Michael P.
Venue: Annual Review of Immunology
Publisher: Annual Reviews
Published: 2020-04-26
Volume: 38
Issue: 1
Pages: 315-340
ISSN: 0732-0582 (ISSN-L)
1545-3278
DOI: 10.1146/annurev-immunol-092419-031130
OpenAlex: W3002478134
Cited by: 464
References: 180
Citations by year: 2026: 101 · 2025: 96 · 2024: 84 · 2023: 55 · 2022: 68 · 2021: 46 · 2020: 14
FWCI: 4.47
Type: journal article
Language: en
Open access: closed
Locations: Annual Review of Immunology (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
Keywords: age-associated B cells, immunosenescence, TLR7 signaling, TLR9 signaling, Th1 cytokines, autoantibodies, autoimmune disease, autoinflammatory disease, aging
MeSH terms: Immunosenescence, Aging, Animals, B-Lymphocytes, Disease Susceptibility, Homeostasis, Humans, Immunologic Memory, Lymphocyte Activation, Biomarkers, Autoimmunity, B-Lymphocyte Subsets, Cytokines

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