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Aging Down-Regulates the Transcription Factor E2A, Activation-Induced Cytidine Deaminase, and Ig Class Switch in Human B Cells
Open accessAbstract
Elderly humans have compromised humoral and cellular immune responses, which lead to reduced protection to infectious agents and to vaccines. Currently, available vaccines suboptimally protect the elderly population. The capacity to class switch the Ig H chain is critical to the effectiveness of humoral immune responses in mice and humans. We have previously shown in mice that the E2A-encoded transcription factor E47, which regulates many B cell functions, is down-regulated in old splenic B cells. This leads to a reduction in the activation-induced cytidine deaminase (AID), which is known to induce class switch recombination and Ig somatic hypermutation. The old activated murine B cells also have less AID and less switched Abs. We have extended our study here to investigate whether aging also affects Ab production and E47 and AID expression in B cells isolated from the peripheral blood of human subjects (18–86 years). Our results obtained with activated CD19+ B cells show that the expression of E47, AID, and Igγ1 circle transcripts progressively decrease with age. We also show an age-related decline in the percentage of switch memory B cells (IgG+/IgA+), an increase in that of naive B cells (IgG−/IgA−/CD27−) for most individuals, and no decrease in that of IgM memory cells in peripheral blood, consistent with our data on the decrease seen in class switch recombination in vitro. Our results provide a possible molecular mechanism for a B cell intrinsic defect in the humoral immune response with aging and suggest avenues for improvement of vaccine response in elderly humans.
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“In view of the critical role played by CD4 + T cells in orchestrating the immune response, some of the age-related deficiencies observed in B cells (51,53,54), which include a reduction in the number of plasmablasts that develop in response to influenza vaccination (55) and the production of poor-quality antibodies to carbohydrate antigens (56)(57)(58), may occur secondary to T cell deficiencies.”
From Causes, consequences, and reversal of immune system aging (2013) · cites this paper as [53]
In the citing paper
“Human and murine B cells also exhibit impaired class switch recombination, which has been attributed to decreased induction of activation-induced cytidine deaminase (AID) enzyme (53).”
From Causes, consequences, and reversal of immune system aging (2013) · cites this paper as [53]
In the citing paper
“The reduced E47 and AID mRNA expression levels in B cells from elderly individuals are due to reduced mRNA stability, which is in turn due to the higher expression of the inflammatory micro-RNAs (miRs) 16 and 155, which bind to the 3’-untranslated region of E47 and AID mRNA, respectively, inducing mRNA degradation [115].”
From Aging of the immune system: Focus on inflammation and vaccination (2016) · cites this paper as [115]
In the citing paper
“E47 mRNA expression has also been shown to be decreased in B cells from elderly individuals [115].”
From Aging of the immune system: Focus on inflammation and vaccination (2016) · cites this paper as [115]
In the citing paper
“The reduced E47 and AID mRNA expression levels in B cells from elderly individuals are due to reduced mRNA stability, which is in turn due to the higher expression of the inflammatory micro-RNAs (miRs) 16 and 155, which bind to the 3’-untranslated region of E47 and AID mRNA, respectively, inducing mRNA degradation [115].”
From Aging of the immune system: Focus on inflammation and vaccination (2016) · cites this paper as [115]
In the citing paper
“Using these markers, it has been shown that the percentage of switched memory B cells, the predictors of optimal antibody responses [114], decreases with age [115, 116].”
From Aging of the immune system: Focus on inflammation and vaccination (2016) · cites this paper as [115]
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1 retracted
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“These changes include shifts in themagnitude of all B cell compartments, specificity repertoire changes, modified peripheral B cell dynamics, and weakened humoral responses (Aberle et al., 2013; Bulati et al., 2011; Faria et al., 2008; Frasca et al., 2008).”
Mechanistic insights into the impairment of memory B cells and antibody production in the elderly
Aberle, J. H., Stiasny, K., Kundi, M., & Heinz, F. X. (2012) · AGE · doi:10.1007/s11357-011-9371-9 · Cited by 50
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“manuscript in preparation) and human [21] B cells.”
Self-citationFrequency and risk factors of low immunoglobulin levels in patients with inflammatory bowel disease
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“…autoimmune diseases (Wehr et al., 2004; Saadoun et al., 2013; Martorana et al., 2014; Adlowitz et al., 2015; Claes et al., 2016; Wang et al., 2018; Golinski et al., 2020), chronic (Moir et al., 2008; Illingworth et al., 2013; Chang et al., 2017), and acute (Woodruff et al., 2020) infectious…”
BackgroundSelf-citationImmunosenescence and multiple sclerosis: inflammaging for prognosis and therapeutic consideration
Thakolwiboon, S., Mills, E. A., Yang, J., Doty, J., Belkin, M., Cho, T., Schultz, C., & Mao‐Draayer, Y. (2023) · Frontiers in Aging · doi:10.3389/fragi.2023.1234572 · Cited by 48
Ageing and obesity similarly impair antibody responses
Frasca, D., Diaz, A., Romero, M., & Blomberg, B. B. (2016) · Clinical & Experimental Immunology · doi:10.1111/cei.12824 · Cited by 43
Self-citationImpact of stress on aged immune system compartments: Overview from fundamental to clinical data
Fali, T., Vallet, H., & Sauce, D. (2018) · Experimental Gerontology · doi:10.1016/j.exger.2018.02.007 · Cited by 46
“Moreover, class switch recombination is impaired in memory B cells with aging (Frasca et al., 2008; Frasca et al., 2012); this may also participate in the decline of the quality of humoral response (Shi et al., 2005).”
BackgroundAge‐related factors that affect B cell responses to vaccination in mice and humans
Frasca, D., Blomberg, B. B., Garcia, D., Keilich, S. R., & Haynes, L. (2020) · Immunological Reviews · doi:10.1111/imr.12864 · Cited by 42
Self-citationZinc deficiency as possible link between immunosenescence and age-related diseases
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“However, a significant reduction in the absolute number of B cells was reported [33], resulting in decreased numbers of B cells in all phenotype subpopulations.”
BackgroundResultEffect of age on surface molecules and cytokine expression in human dendritic cells
Ciaramella, A., Spalletta, G., Bizzoni, F., Salani, F., Caltagirone, C., & Bossù, P. (2011) · Cellular Immunology · doi:10.1016/j.cellimm.2011.04.010 · Cited by 43
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Obesity Accelerates Age Defects in Mouse and Human B Cells
Frasca, D., & Blomberg, B. B. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.02060 · Cited by 42
“These results recapitulate what we have initially shown in our studies on the effects of aging on B cell function in which both AID and E47 were found decreased in mitogen-stimulated B cells from elderly as compared to young individuals (64).”
ResultSelf-citationAging and respiratory viral infection: from acute morbidity to chronic sequelae
Wu, Y., Goplen, N. P., & Sun, J. (2021) · Cell & Bioscience · doi:10.1186/s13578-021-00624-2 · Cited by 42
“Upon in vitro stimulation of anti-CD40/IL-4, the production of IgG decreased with age in B cells, indicating that class-switch recombination (CSR) declines with age [50].”
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van den Hoogen, L. L., Sims, G. P., van Roon, J. A. G., & Fritsch-Stork, R. D. E. (2015) · Current Aging Science · doi:10.2174/1874609808666150727111904 · Cited by 40
van Opstal, E. J., Kolling, G. L., Moore, J. H., Coquery, C. M., Wade, N. S., Loo, W. M., Bolick, D. T., Shin, J. H., Erickson, L. D., & Warren, C. A. (2016) · The Journal of Infectious Diseases · doi:10.1093/infdis/jiw071 · Cited by 39
“of high affinity IgG, IgA, and IgE.[15] Serum IgA levels are elevated in the elderly as compared with younger controls, but these IgA are predominantly monomeric IgA which are not transported to the mucosal surface as sIgA.”
BackgroundAntibody-Dependent Cellular Cytotoxicity Responses to Seasonal Influenza Vaccination in Older Adults
Vanderven, H. A., Jegaskanda, S., Wines, B. D., Hogarth, P. M., Carmuglia, S., Rockman, S. P., Chung, A. W., & Kent, S. J. (2017) · The Journal of Infectious Diseases · doi:10.1093/infdis/jix554 · Cited by 40
“Older adults have decreased generation of memory B cells, longlived plasma cells, and serum antibodies [13, 14].”
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The impact of immuno-aging on SARS-CoV-2 vaccine development
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Age‐related aspects of human IgM+ B cell heterogeneity
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“Furthermore, a decrease in classswitched B cells and decrease in affinity antibodies has been observed in the elderly (Frasca et al. 2008).”
BackgroundHuman immune phenotyping reveals accelerated aging in type 1 diabetes
Shapiro, M. R., Dong, X., Perry, D. J., McNichols, J., Thirawatananond, P., Posgai, A. L., Peters, L. D., Motwani, K., Musca, R. S., MUIR, A. B., et al. (2023) · JCI Insight · doi:10.1172/jci.insight.170767 · Cited by 36
“As summarized in Figure 5, we found an association of increasing non-class-switched memory B cells with age, while transitional B cells declined with both aging and T1D (48, 49).”
Obesity accelerates age defects in B cells, and weight loss improves B cell function
Frasca, D., Romero, M., Diaz, A., & Blomberg, B. B. (2023) · Immunity & Ageing · doi:10.1186/s12979-023-00361-9 · Cited by 36
Self-citationQuantity, not quality, of antibody response decreased in the elderly
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Self-citationSystems Biology of Vaccination in the Elderly
Duraisingham, S., Rouphael, N., Cavanagh, M., Nakaya, H. I., Goronzy, J. J., & Pulendran, B. (2012) · Current topics in microbiology and immunology · doi:10.1007/82_2012_250 · Cited by 34
Rebalancing the unbalanced aged immune system – A special focus on zinc
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Lee, J. L., Fra-Bidó, S., Burton, A. R., Innocentin, S., Hill, D. L., & Linterman, M. A. (2022) · Aging Cell · doi:10.1111/acel.13692 · Cited by 34
“…age- related cell- intrinsic defects in human B cell proliferation and differentiation into plasma cells, we did observe a decrease in the percentage of B cells in the peripheral blood of older donors compared to younger donors, as previously reported (Frasca et al., 2008; Frasca & Blomberg, 2009).”
BackgroundResultMuggen, A. F., de Jong, M. M. E., Wolvers-Tettero, I. L. M., Kallemeijn, M. J., Teodósio, C., Darzentas, N., Stadhouders, R., IJspeert, H., van der Burg, M., van IJcken, W. F. J., et al. (2019) · Immunity & Ageing · doi:10.1186/s12979-019-0163-x · Cited by 32
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Age-Related Cognitive Decline and Dementia: Interface of Microbiome–Immune–Neuronal Interactions
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Aging impairs murine B cell differentiation and function in primary and secondary lymphoid tissues.
Frasca, D., & Blomberg, B. B. (2011) · Europe PMC (PubMed Central) · Cited by 31
Self-citationImmune profiling by multiple gene expression analysis in patients at-risk and with type 1 diabetes
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Self-citationMEF2C protects bone marrow B-lymphoid progenitors during stress haematopoiesis
Wang, W., Org, T., Montel‐Hagen, A., Pioli, P. D., Duan, D., Israely, E., Malkin, D. J., Su, T., Flach, J., Kurdistani, S. K., et al. (2016) · Nature Communications · doi:10.1038/ncomms12376 · Cited by 30
Early Highly Active Antiretroviral Therapy Enhances B-cell Longevity
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Cellular senescence is a key mediator of lung aging and susceptibility to infection
Torrance, B. L., & Haynes, L. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1006710 · Cited by 28
“This was also observed in B cells isolated from older adults (59).”
ResultPremature B-cell senescence as a consequence of chronic immune activation
Palma, P., Rinaldi, S., Cotugno, N., Santilli, V., Pahwa, S. G., Rossi, P., & Cagigi, A. (2014) · Human Vaccines & Immunotherapeutics · doi:10.4161/hv.28698 · Cited by 29
Multiple Levels of Immunological Memory and Their Association with Vaccination
Bugya, Z., Prechl, J., Szénási, T., Nemes, É., Bácsi, A., & Koncz, G. (2021) · Vaccines · doi:10.3390/vaccines9020174 · Cited by 30
“Reduced function of TFH cells, decreased production of AID and impaired immune-complex retention of FDC compromise memory B cell functions [41,122] and consequently limits optimal plasma cell formation [165].”
BackgroundAn old problem with new solutions: Strategies to improve vaccine efficacy in the elderly
Bell, M. R., & Kutzler, M. A. (2022) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2022.114175 · Cited by 29
Ageing impairs the T cell response to dendritic cells
You, J., Dong, H., Mann, E. R., Knight, S. C., & Yaqoob, P. (2013) · Immunobiology · doi:10.1016/j.imbio.2013.02.002 · Cited by 28
DiMenna, L. J., Latimer, B. P., Parzych, E. M., Haut, L. H., Töpfer, K., Abdulla, S., Yu, H. B., Manson, B., Giles‐Davis, W., Zhou, D., et al. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.0903808 · Cited by 28
“not in mice numbers of B cells decline in the periphery on aging (3).”
BackgroundDavydov, A. N., Obraztsova, A., Lebedin, M. Y., Turchaninova, M. A., Staroverov, D. B., Merzlyak, E. M., Sharonov, G. V., Кладова, О. В., Shugay, M., Britanova, O. V., et al. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.02309 · Cited by 29
“Of note, it was earlier demonstrated that AID levels and intensity of hypermutation decrease with aging, but only after the age of 60 (63, 69, 70)—beyond the age of the cohorts that we have studied in the current work.”
BackgroundCarney, E. F., Srinivasan, V., Moss, P. A., & Taylor, A. M. (2012) · The Journal of Immunology · doi:10.4049/jimmunol.1101909 · Cited by 26
“Interestingly, both A-T patients (19) and the elderly normal population (20) have low thymic output and elevated levels of oxidative stress, and both normal elderly (21, 22) and some A-T patients show decreased production”
BackgroundNanovaccines for Advancing Long-Lasting Immunity against Infectious Diseases
Gao, X., Wang, X., Li, S., Rahman, M. S. U., Xu, S., & Liu, Y. (2023) · ACS Nano · doi:10.1021/acsnano.3c07741 · Cited by 27
Management of the Elderly Patients with Inflammatory Bowel Disease
Katz, S., Surawicz, C. M., & Pardi, D. S. (2013) · Inflammatory Bowel Diseases · doi:10.1097/mib.0b013e31828c8536 · Cited by 26
The role of autoantibodies in bridging obesity, aging, and immunosenescence
Valentino, T. R., Chen, N., Makhijani, P., Khan, S. M., Winer, S., Revelo, X. S., & Winer, D. A. (2024) · Immunity & Ageing · doi:10.1186/s12979-024-00489-2 · Cited by 27
“The decrease in E47 and AID was associated with remarkably lower levels of memory B cells, and higher percentage of naive B cells [117].”
B Cells Dynamic in Aging and the Implications of Nutritional Regulation
Yu, Y., Lu, C., Yu, W., Lei, Y., Sun, S., Liu, P., Bai, F., Chen, Y., & Chen, J. (2024) · Nutrients · doi:10.3390/nu16040487 · Cited by 29
“Frasca reported a reduced frequency of MZ B cells in old mice, with 65% of them lower than all young mice, and some showing extremely low spleen MZ B cells [36].”
BackgroundFeng, R., Zhao, J., Sun, F., Miao, M., Sun, X., He, J., & Li, Z. (2022) · Annals of Medicine · doi:10.1080/07853890.2022.2031272 · Cited by 24
Analysis of Immune and Inflammation Characteristics of Atherosclerosis from Different Sample Sources
NIE, H., Chen, Y., Zhou, W., & Li, T. (2022) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2022/5491038 · Cited by 24
“…reduced in the bone marrow of aged mice and humans [48], Frasca et al. found that aging downregulates B cell type switching in humans and mice [49]; in addition, hypercholesterolemia Apoe-/- mice and low-density lipoprotein-de fi cient mice have also shown that protective immunity of B cells…”
Jensen, K., Brusletto, B. S., Aass, H. C. D., Olstad, O. K., Kierulf, P., & Gautvik, K. M. (2013) · PLoS ONE · doi:10.1371/journal.pone.0070721 · Cited by 24
“alterations both in key proteins driving the differentiation [2–7], and to modification in the supporting microenvironment [8,9].”
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Centenarian Offspring: A Model for Understanding Longevity
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“However, a serum increase of switched immunoglobulins and a reciprocal decrease of both serum IgM and IgD have been demonstrated in elderly people [45-47].”
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“…regulatory region, which may influence the transcription (http://fastsnp.ibms.sinica.edu.tw). a SNPs were intronic enhancers of the gene. regulation of TCF3 gene usually happened in the old B cells or elderly people, which indicated the reduced protection to infectious agents (Frasca et al. 2008).”
InfluentialHe, X.-S., Sasaki, S., Baer, J., Khurana, S., Golding, H., Treanor, J. J., Topham, D. J., Sangster, M. Y., Jin, H., Dekker, C. L., et al. (2012) · The Journal of Infectious Diseases · doi:10.1093/infdis/jis664 · Cited by 22
“with age [19, 20] and is associated with a reduced serum antibody response to seasonal influenza vaccination in elderly individuals [21].”
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“immune remodeling, which occurs when innate barriers lose their abilities to restrict pathogen entry; in this condition, the internal organs become more vulnerable to metabolic disturbances resulting in a natural reduction in life expectancy [6, 7].”
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“…in elderly Frontiers in Aging | www.frontiersin.org December 2021 | Volume 2 | Article 7485917 populations as bonemarrow is degraded, and also the percentages and quantities of human peripheral B cells significantly reduced with age (Zharhary, 1988; Rossi et al., 2003; Frasca et al., 2008).”
BackgroundJu, C., Blum, L. K., Kongpachith, S., Lingampalli, N., Mao, R., Brodin, P., Dekker, C. L., Davis, M. M., & Robinson, W. H. (2018) · Clinical Immunology · doi:10.1016/j.clim.2018.01.011 · Cited by 21
Rožman, P. J. (2018) · GeroScience · doi:10.1007/s11357-018-0027-x · Cited by 20
Biological Effects of Calorie Restriction: Implications for Modification of Human Aging
Spindler, S. R. (2010) · Springer eBooks · doi:10.1007/978-90-481-3999-6_12 · Cited by 20
“Lymphocytes from older humans have impaired ability to undergo immunoglobulin class-switching recombination (Frasca et al. 2008).”
BackgroundImmune response to COVID-19 in older adults
Jergović, M., Coplen, C. P., Uhrlaub, J. L., & Nikolich‐Žugich, J. (2021) · The Journal of Heart and Lung Transplantation · doi:10.1016/j.healun.2021.04.017 · Cited by 20
Baseline immune states (BIS) associated with vaccine responsiveness and factors that shape the BIS
Nehar-Belaid, D., Sokolowski, M. J., Ravichandran, S., Banchereau, J., Chaussabel, D., & Ucar, D. (2023) · Seminars in Immunology · doi:10.1016/j.smim.2023.101842 · Cited by 19
Reduction in ocrelizumab-induced infusion reactions by a modified premedication protocol
Conte, W. L., Arndt, N., Cipriani, V., Dellaria, A., & Javed, A. (2018) · Multiple Sclerosis and Related Disorders · doi:10.1016/j.msard.2018.11.027 · Cited by 21
Jergović, M., Uhrlaub, J. L., Watanabe, M., Bradshaw, C. M., White, L. M., LaFleur, B., Edwards, T., Sprissler, R. S., Worobey, M., Bhattacharya, D., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-30617-9 · Cited by 21
Age-related changes in the transcriptome of antibody-secreting cells
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“Class switching [41] and hypermutation of immunoglobulin genes [42] are also diminished resulting in the production of low affinity antibodies.”
Ju, Z., Zhang, X., Wang, J., Cheng, X., Zhang, Y., & Zhou, W. (2020) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.00350 · Cited by 19
“, 2014); T-cell deficiency leads to cognitive decline, and it also decreases the ability of T cell to assist B-cell activation and antibody production with aging (Saurwein-Teissl et al., 2002; Frasca et al., 2008).”
BackgroundAging and neoteny in the B lineage
Melamed, D., & Scott, D. W. (2012) · Blood · doi:10.1182/blood-2012-07-444711 · Cited by 19
Breakthrough COVID-19 Infections in the US: Implications for Prolonging the Pandemic
Alcendor, D. J., Matthews-Juarez, P., Smoot, D. T., Hildreth, J. E. K., Lamar, K. D., Tabatabai, M., Wilus, D. M., & Juárez, P. D. (2022) · Vaccines · doi:10.3390/vaccines10050755 · Cited by 18
“In addition, follicular CD4 T-cell functions that are suboptimal for proper B-cell maturation play a role in changes that may occur regarding antibody production [79].”
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SNPs in DNA repair genes associated to meningitis and host immune response
da Silva, T. A., Fontes-Dantas, F. L., Coutinho, L. G., de Souza, F. R. S., Campos, J. T. A. D. M., de Souto, J. T., Leib, S. L., & Agnez‐Lima, L. F. (2011) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/j.mrfmmm.2011.05.012 · Cited by 18
Immunity to acute virus infections with advanced age
Nikolich‐Žugich, J., Bradshaw, C. M., Uhrlaub, J. L., & Watanabe, M. (2020) · Current Opinion in Virology · doi:10.1016/j.coviro.2020.09.007 · Cited by 19
“somatic hypermutation[55], resulting in inferior antibody responses.”
Fotopoulou, F., Rodriguez-Correa, E., Dussiau, C., & Milsom, M. D. (2024) · Experimental Hematology · doi:10.1016/j.exphem.2024.104698 · Cited by 17
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“The percentage and numbers of total B cells, as defined by CD19 expression, decrease with age [65-67].”
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“The ability of B-cells to express AID decreases with age [6,7] and interestingly, the decreased AID expression in the elderly has recently been shown to relate to a decreased antibody response to A(H1N1)pdm09 vaccination as compared with healthy young individuals [20,21].”
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Glucocorticoid inhibition of activation-induced cytidine deaminase expression in human B lymphocytes
Benko, A. L., Olsen, N. J., & Kovacs, W. J. (2013) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2013.11.001 · Cited by 16
“A c1/2-Cl circle transcript standard was prepared by amplification of cDNA from activated human B lymphocytes using primers previously described for semi-quantitative assays (Cerutti et al., 2002; Frasca et al., 2008).”
Aging and Microbiome in the Modulation of Vaccine Efficacy
Kumar, M., James, M. M., Kumawat, M., Nabi, B., Sharma, P., Pal, N., Shubham, S., Tiwari, R. R., Sarma, D. K., & Nagpal, R. (2022) · Biomedicines · doi:10.3390/biomedicines10071545 · Cited by 15
“While the fraction of IgM+ memory B-cells appears to remain constant with age, the number and percentage of IgG+ and IgA+ B-cells and plasma blasts (PB) decrease dramatically [59].”
BackgroundSystemic immunometabolism and responses to vaccines: insights from T and B cell perspectives
Nettelfield, S., Yu, D., & Cañete, P. F. (2023) · International Immunology · doi:10.1093/intimm/dxad021 · Cited by 15
The immunosenescence clock: A new method for evaluating biological age and predicting mortality risk
Li, S., Wang, K., Wu, J., & Zhu, Y. (2024) · Ageing Research Reviews · doi:10.1016/j.arr.2024.102653 · Cited by 18
“…NK cells expands dramatically, with increases in the expression of CD57, killer cell immunoglobulin-like receptor (KIR) and leukocyte immunoglobulin-like receptor (ILT-2) on the cell surface (Borrego et al., 1999, Chi-drawar et al., 2006, Frasca et al., 2008, Le Garff-Tavernier et al., 2010).”
Perspectives on vaccine development for the elderly
Oviedo‐Orta, E., Li, C. K.-F., & Rappuoli, R. (2013) · Current Opinion in Immunology · doi:10.1016/j.coi.2013.07.008 · Cited by 15
“In memory responses, switched memory B cells decline in numbers but memory T cells ‘inflate’ in numbers [20,21].”
Human hematopoiesis: aging and leukemogenic risk
Adelman, E. R., & Figueroa, M. E. (2020) · Current Opinion in Hematology · doi:10.1097/moh.0000000000000622 · Cited by 15
“have reduced specificity and affinity for their target antigens [12,13].”
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“Although several studies have established a defect in immune responses to vaccination in the elderly (18, 22, 23, 49), we sought to evaluate the durability and efficacy of immune responses initially elicited in young animals.”
BackgroundKardava, L., Yang, Q., Leger, A. J. S., Foon, K. A., Lentzsch, S., Vallejo, A. N., Milcarek, C., & Borghesi, L. (2011) · International Immunology · doi:10.1093/intimm/dxr027 · Cited by 15
Older Human B Cells and Antibodies
Dunn‐Walters, D. K., & O’Hare, J. S. (2017) · Springer eBooks · doi:10.1007/978-3-319-64597-1_21-1 · Cited by 14
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“…in adaptive immunity as they age, including reduced production of common lymphoid precursors in the bone marrow, thymic involution resulting in decreased T cell output, and a reduction in the breadth and distribution of the naive T cell repertoire [69, 70] and reduced numbers of B cells [71, 72].”
Immunosenescence and the Geriatric Giants: Molecular Insights into Aging and Healthspan
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“These breaks are then repaired through non-homologous end joining, enabling the recombination of different constant-region genes with the variable region, thus changing the antibody isotype while preserving antigen specificity [57].”
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B cells from old mice induce the generation of inflammatory T cells through metabolic pathways
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“At the age of 15–49 the reported cure rate is approximately 75%, but falls to 52% for those aged 75 and over [173] In a similar process to that seen in VDJ recombinase activity and B ALL cure rates, the level of activity of SMH system has been demonstrated to fall dramatically in B cells with increasing patient age an…”
BackgroundRivera-Carranza, T., Nájera-Medina, O., Bojalil‐Parra, R., Rodríguez-López, C. P., Zúñiga-León, E., Girón, A. L.-T., & Azaola‐Espinosa, A. (2023) · PeerJ · doi:10.7717/peerj.15465 · Cited by 13
Metadata
- Authors
- Frasca, D., Landin, A. M., Lechner, S. C., Ryan, J. G., Schwartz, R., Riley, R. L., & Blomberg, B. B.
- Affiliations
- University of Miami (US)
- Corresponding author
- Frasca, Daniela
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2008-04
- Volume
- 180
- Issue
- 8
- Pages
- 5283-5290
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1480510972
- Cited by
- 333
- References
- 49
- Citations by year
- 2026: 13 · 2025: 14 · 2024: 8 · 2023: 24 · 2022: 24 · 2021: 23 · 2020: 23 · 2019: 18 · 2018: 16 · 2017: 18 · 2016: 20 · 2015: 16 · 2014: 14 · 2013: 32 · 2012: 21
- FWCI
- 6.81
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (AG-17618, R01AG017618, R37AG023717, AG-28586, AG23717, R21AG028586, R01AG025256, AG-025256)
- National Institute of Allergy and Infectious Diseases (AI 064591, R01AI064591)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Life Sciences › Immunology and Microbiology › Immunology › Immunodeficiency and Autoimmune Disorders
- Keywords
- immunosenescence, B cell aging, E2A transcription factor, E47, activation-induced cytidine deaminase, class switch recombination, IgG1, naive B cells, humoral immune response, vaccine response in the elderly
- MeSH terms
- AICDA (Activation-Induced Cytidine Deaminase), Adolescent, Adult, Aged, Aged, 80 and over, Aging, B-Lymphocytes, Cells, Cultured, Cytidine Deaminase, Female, Humans, Immunologic Memory, Lymphocyte Activation, Male, Middle Aged, Gene Rearrangement, B-Lymphocyte, Down-Regulation, Immunoglobulin Class Switching, Basic Helix-Loop-Helix Proteins
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