The generation of memory B cells is maintained, but the antibody response is not, in the elderly after repeated influenza immunizations
Open accessAbstract
The success of a vaccine in inducing a protective antibody response depends on the longevity of both long-lived plasma cells (PC) and memory B cells. We have previously shown that the in vivo antibody response to a new influenza vaccine, the ex vivo plasmablast response, the in vitro B cell function, measured by AID (activation-induced cytidine deaminase), and the transcription factor E47, are significantly associated and decreased in elderly individuals. We hypothesized that because AID is decreased in the elderly, the ability to generate memory B cells would also be decreased, but our findings here show that memory B cells are maintained in the elderly probably due to further amplification in response to repeated vaccination. We recruited young and elderly individuals immunized in at least two consecutive influenza vaccine seasons in which the influenza A viral strains H1N1 and H3N2 in the vaccine were the same as in the previous year. PBMC were cultured with CpG/IL2 to measure the frequency of IgG vaccine-specific memory B cells. Serum antibody response was measured by hemagglutination inhibition assay. Blood plasmablasts were measured by flow cytometry. Surprisingly, the frequencies of influenza vaccine-specific memory B cells and plasmablasts were similar in young and elderly individuals, but the fold-increase in serum titers after vaccination was lower in the elderly although most of the elderly were seroprotected. We then measured the transcription factor Blimp-1, considered the master regulator of PC differentiation, and found it significantly reduced in cultures of B cells from elderly versus young individuals, as well as E47/AID and IgG secretion. Taken together, these results suggest an impaired memory B cell to PC differentiation in the elderly.
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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 [73]
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 [73]
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 [73]
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- Authors
- Frasca, D., Diaz, A., Romero, M., & Blomberg, B. B.
- Affiliations
- University of Miami (US)
- Corresponding author
- Frasca, Daniela
- Venue
- Vaccine
- Publisher
- Elsevier BV
- Published
- 2016-05
- Volume
- 34
- Issue
- 25
- Pages
- 2834-2840
- ISSN
- 0264-410X (ISSN-L)
- PMC
- PMC4876633
- OpenAlex
- W2341732428
- Cited by
- 144
- References
- 39
- Citations by year
- 2026: 8 · 2025: 18 · 2024: 13 · 2023: 11 · 2022: 16 · 2021: 28 · 2020: 20 · 2019: 12 · 2018: 7 · 2017: 9 · 2016: 2
- FWCI
- 9.38
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Vaccine (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIH (AI096446, AG042826, AG032576)
- Topics
- Health Sciences › Medicine › Epidemiology › Influenza Virus Research Studies
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Keywords
- memory B cells, influenza vaccination, older adults, long-lived plasma cells, plasmablasts, activation-induced cytidine deaminase, Blimp-1, E47, B cell differentiation, antibody response, age-related immunosenescence, hemagglutination inhibition, repeated vaccination
- MeSH terms
- Positive Regulatory Domain I-Binding Factor 1, Adult, Aged, Antibodies, Viral, Antibody Formation, B-Lymphocytes, Cell Differentiation, Female, Hemagglutination Inhibition Tests, Humans, Immunoglobulin G, Immunologic Memory, Influenza, Human, Influenza Vaccines, Male, Middle Aged, Plasma Cells, Repressor Proteins, Influenza A Virus, H1N1 Subtype, Influenza A Virus, H3N2 Subtype
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