Reduced Ig class switch in aged mice correlates with decreased E47 and activation-induced cytidine deaminase
Open accessAbstract
The capacity to class switch the IgH chain is critical to the effectiveness of humoral immune responses. We show that in vitro-stimulated splenic B cells from senescent mice are deficient in production of multiple class switch isotypes (IgG1, G2a, G3, and E), class switch recombination (CSR), and induction of the E2A-encoded transcription factor E47. E47 has previously been shown to be required for CSR, at least in part via expression of the activation-induced cytidine deaminase. Our studies show that impaired induction of E47, and subsequently activation-induced cytidine deaminase, contribute to poor CSR and production of secondary isotypes in senescence.
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E47 is the key transcription factor for the induction of activation-induced cytidine deaminase (AID), involved in class switching and somatic hypermutation.
“This is the key transcription factor, for the induction of activation-induced cytidine deaminase (AID), involved in class switching and somatic hypermutation.”
From Immunosenescence and Its Hallmarks: How to Oppose Aging Strategically? A Review of Potential Options for Therapeutic Intervention (2019) · cites this paper as [72]
The reduced expression of E2A might be responsible for the decreased avidity of antibodies and diminished antibody-mediated protection.
“The reduced expression of E2A might be responsible for the decreased avidity of antibodies and diminished antibody-mediated protection (72, 73).”
From Immunosenescence and Its Hallmarks: How to Oppose Aging Strategically? A Review of Potential Options for Therapeutic Intervention (2019) · cites this paper as [72]
Activated B cells isolated from older adults display a reduced induction of E47, a class I basic helix-loop-helix protein encoded by the E2A gene.
“Activated B cells isolated from older adults display a reduced induction of E47, a class I basic helix-loop-helix protein encoded by the E2A gene.”
From Immunosenescence and Its Hallmarks: How to Oppose Aging Strategically? A Review of Potential Options for Therapeutic Intervention (2019) · cites this paper as [72]
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- Authors
- Frasca, D., Van der Put, E., Riley, R. L., & Blomberg, B. B.
- Affiliations
- University of Miami (US)
- Department of Microbiology and Immunology, University of Miami School of Medicine , Miami, FL 33136
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2004-02
- Volume
- 172
- Issue
- 4
- Pages
- 2155-2162
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W2102243911
- Cited by
- 150
- References
- 50
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 7 · 2023: 13 · 2022: 11 · 2021: 15 · 2020: 9 · 2019: 8 · 2018: 3 · 2017: 4 · 2016: 1 · 2015: 2 · 2014: 5 · 2013: 8 · 2012: 7
- FWCI
- 1.68
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (1r01ag015474-01)
- National Institute on Aging (AG-17618, R01AG017618, AG-15474)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Immunology and Microbiology › Immunology › Immunodeficiency and Autoimmune Disorders
- Keywords
- immunosenescence, class switch recombination, E47, E2A transcription factor, activation-induced cytidine deaminase, B cells, IgG isotypes, IgE, splenic B cells, aged mice, humoral immune response
- MeSH terms
- AICDA (Activation-Induced Cytidine Deaminase), Aging, Animals, Cells, Cultured, Cytidine Deaminase, DNA, DNA-Binding Proteins, Enzyme Induction, Female, Heterozygote, Immunoglobulin E, Immunoglobulin G, Lymphocyte Activation, Male, Mice, Inbred BALB C, Mice, Inbred C57BL, Protein Binding, Recombination, Genetic, Spleen, Transcription Factors, Transcription, Genetic, Down-Regulation, Interleukin-4, B-Lymphocyte Subsets, Cellular Senescence, Immunoglobulin Class Switching, CD40 Antigens, Mice, TCF Transcription Factors, Transcription Factor 7-Like 1 Protein
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