Senescent B cells in aging and age-related diseases: Their role in the regulation of antibody responses

Frasca, Daniela

doi:10.1016/j.exger.2017.07.002

Cited by 82Telomeres, Telomerase, and SenescenceT-cell and B-cell ImmunologyGenetics, Aging, and Longevity in Model Organisms

Senescent B cells in aging and age-related diseases: Their role in the regulation of antibody responses

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Frasca, Daniela·2018·Experimental Gerontology

DOI 10.1016/j.exger.2017.07.002PMC PMC5754260

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Abstract

Immune cells with a senescence-associated secretory phenotype increase in the blood of elderly individuals or individuals with age-associated diseases or with infections. Although senescent immune cells do not proliferate, they are transcriptionally and metabolically active and affect the microenvironment through the secretion of pro-inflammatory mediators. An age-driven increase in senescent B, T and NK cells has been reported and the function of these cells has been characterized. Results published by different groups have demonstrated that cell senescence induces the accumulation of terminally-differentiated cells characterized by the arrest of cell proliferation but with an active secretory profile which regulates their function through the activation of pathways integrating senescence and energy-sensing signals. This review will focus on senescent B cells, their increase in aging, age-associated conditions and infections. Similarities with other senescent immune cells will be presented and discussed.

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T cell populations exhibiting multiple senescence markers and lacking proliferative capacity, B cells, and monocytes with senescent features have been described and implicated in immunopathology.
“T cell populations exhibiting multiple senescence markers and lacking proliferative capacity, in addition to B cells (30) and monocytes (31) that carry senescent features, have been described (32) and implicated in immunopathology.”
From Connecting aging biology and inflammation in the omics era (2022) · cites this paper as [30]
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 [157]
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 [157]
Human age-associated B cells secrete inflammatory mediators such as TNFα, IL-6, and IL-8.
“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 [157]

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Inflamm‐aging: An Evolutionary Perspective on Immunosenescence
FRANCESCHI, C., BONAFÈ, M., VALENSIN, S., OLIVIERI, F., DE LUCA, M., OTTAVIANI, E., & DE BENEDICTIS, G. (2000) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2000.tb06651.x · Cited by 5,358 · see citing works
Inflammation in Atherosclerosis
Libby, P. (2012) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.108.179705 · Cited by 3,748 · see citing works
The CD28 Signaling Pathway Regulates Glucose Metabolism
Frauwirth, K. A., Riley, J. L., Harris, M. H., Parry, R. V., Rathmell, J. C., Plas, D. R., Elstrom, R. L., June, C. H., & Thompson, C. B. (2002) · Immunity · doi:10.1016/s1074-7613(02)00323-0 · Cited by 1,475 · see citing works
Inflammatory networks during cellular senescence: causes and consequences.
Freund, A., Orjalo, A. V., Desprez, P.-Y., & Campisi, J. (2010) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2010.03.003 · Cited by 1,354 · see citing works
Systemic inflammation and disease progression in Alzheimer disease
Holmes, C., Cunningham, C., Zotova, E., Woolford, J., Dean, C., Kerr, S., Culliford, D., & Perry, V. H. (2009) · Neurology · doi:10.1212/wnl.0b013e3181b6bb95 · Cited by 1,139 · see citing works
Evidence for HIV-associated B cell exhaustion in a dysfunctional memory B cell compartment in HIV-infected viremic individuals
Moir, S. L., Ho, J., Malaspina, A., Wang, W., DiPoto, A. C., O’Shea, M. A., Roby, G. A., Kottilil, S., Arthos, J. A., Proschan, M. A., et al. (2008) · The Journal of Experimental Medicine · doi:10.1084/jem.20072683 · Cited by 894 · see citing works
Metabolic Reprogramming Is Required for Antibody Production That Is Suppressed in Anergic but Exaggerated in Chronically BAFF-Exposed B Cells
Caro‐Maldonado, A., Wang, R., Nichols, A., Kuraoka, M., Milasta, S., Sun, L., Gavin, A. L., Abel, E. D., Kelsoe, G. H., Green, D. R., et al. (2014) · The Journal of Immunology · doi:10.4049/jimmunol.1302062 · Cited by 553 · see citing works
Osteoporosis and Inflammation
Mundy, G. R. (2008) · Nutrition Reviews · doi:10.1111/j.1753-4887.2007.tb00353.x · Cited by 480 · see citing works
AMP kinase and malonyl-CoA: targets for therapy of the metabolic syndrome
Ruderman, N., & Prentki, M. (2004) · Nature Reviews Drug Discovery · doi:10.1038/nrd1344 · Cited by 451 · see citing works
Osteoporosis and Inflammation
Mundy, G. R. (2007) · Nutrition Reviews · doi:10.1301/nr.2007.dec.s147-s151 · Cited by 408 · see citing works
p38 signaling inhibits mTORC1-independent autophagy in senescent human CD8+ T cells
Henson, S. M., Lanna, A., Riddell, N. E., Franzese, O., Macaulay, R., Griffiths, S. J., Puleston, D. J., Watson, A. S., Simon, A. K., Tooze, S. A., et al. (2014) · Journal of Clinical Investigation · doi:10.1172/jci75051 · Cited by 389 · see citing works
Cellular senescence: putting the paradoxes in perspective
Campisi, J. (2011) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2010.10.005 · Cited by 368 · see citing works
Inflammaging decreases adaptive and innate immune responses in mice and humans
Frasca, D., & Blomberg, B. B. (2016) · Biogerontology · doi:10.1007/s10522-015-9578-8 · Cited by 357 · see citing works
Self-citation
Visceral adipose tissue as a source of inflammation and promoter of atherosclerosis
Alexopoulos, N. A., Katritsis, D. G., & Raggi, P. (2014) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2013.12.023 · Cited by 333 · see citing works
Malaria-associated atypical memory B cells exhibit markedly reduced B cell receptor signaling and effector function
Portugal, S., Tipton, C. M., Sohn, H., Koné, Y., Wang, J., Li, S., Skinner, J., Virtaneva, K. I., Sturdevant, D. E., Porcella, S. F., et al. (2015) · eLife · doi:10.7554/elife.07218 · Cited by 330 · see citing works
The kinase p38 activated by the metabolic regulator AMPK and scaffold TAB1 drives the senescence of human T cells
Lanna, A., Henson, S. M., Escors, D., & Akbar, A. N. (2014) · Nature Immunology · doi:10.1038/ni.2981 · Cited by 328 · see citing works
A new CD21low B cell population in the peripheral blood of patients with SLE
Wehr, C., Eibel, H., Masilamani, M., Illges, H., Schlesier, M., Peter, H., & Warnatz, K. (2004) · Clinical Immunology · doi:10.1016/j.clim.2004.05.010 · Cited by 308 · see citing works
Activated memory B cell subsets correlate with disease activity in systemic lupus erythematosus: delineation by expression of CD27, IgD, and CD95.
Jacobi, A., Reiter, K., Mackay, M., Aranow, C., Hiepe, F., Radbruch, A., Hansen, A., Burmester, G., Diamond, B., Lipsky, P., et al. (2008) · Arthritis & Rheumatism · doi:10.1002/art.23498 · Cited by 300 · see citing works
Chronic Exposure to Plasmodium falciparum Is Associated with Phenotypic Evidence of B and T Cell Exhaustion
Illingworth, J. J., Butler, N. S., Roetynck, S., Mwacharo, J., Pierce, S. K., Bejon, P., Crompton, P. D., Marsh, K., & Ndungu, F. M. (2012) · The Journal of Immunology · doi:10.4049/jimmunol.1202438 · Cited by 290 · see citing works
A double-negative (IgD−CD27−) B cell population is increased in the peripheral blood of elderly people
Colonna-Romano, G., Bulati, M., Aquino, A., Pellicanò, M., Vitello, S., Lio, D., Candore, G., & Caruso, C. (2009) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2009.08.003 · Cited by 270 · see citing works
Impact of cellular senescence signature on ageing research
Sikora, E., Arendt, T., Bennett, M., & Narita, M. (2011) · Ageing Research Reviews · doi:10.1016/j.arr.2010.10.002 · Cited by 264 · see citing works
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Rubtsov, A. V., Rubtsova, K., Kappler, J. W., Jacobelli, J., Friedman, R. S., & Marrack, P. (2015) · The Journal of Immunology · doi:10.4049/jimmunol.1500055 · Cited by 235 · see citing works
Expansion of Autoreactive Unresponsive CD21−/low B Cells in Sjögren's Syndrome–Associated Lymphoproliferation
Saadoun, D., Terrier, B., Bannock, J. M., Vazquez, T., Massad, C., Kang, I., Joly, F., Rosenzwajg, M., Sène, D., Benech, P. D., et al. (2012) · Arthritis & Rheumatism · doi:10.1002/art.37828 · Cited by 230 · see citing works
Obesity decreases <scp>B</scp> cell responses in young and elderly individuals
Frasca, D., Ferracci, F., Diaz, A., Romero, M., Lechner, S., & Blomberg, B. B. (2016) · Obesity · doi:10.1002/oby.21383 · Cited by 228 · see citing works
Self-citation
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Claes, N., Fraussen, J., Vanheusden, M., Hellings, N., Stinissen, P., Wijmeersch, B. V., Hupperts, R., & Somers, V. A. (2016) · The Journal of Immunology · doi:10.4049/jimmunol.1502448 · Cited by 206 · see citing works
Human peripheral late/exhausted memory B cells express a senescent-associated secretory phenotype and preferentially utilize metabolic signaling pathways
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Self-citation
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Henson, S. M., Macaulay, R., Riddell, N. E., Nunn, C. J., & Akbar, A. N. (2015) · European Journal of Immunology · doi:10.1002/eji.201445312 · Cited by 146 · cited 2× · see citing works
“Similar to LM B cells, terminally-differentiated CD4+ T cells (Henson et al., 2014; Henson et al., 2015; Lanna et al., 2014) show spontaneous activation of AMPKwhich leads to the recruitment of p38MAPK to the scaffold protein TAB1 and consequent p38MAPK phosphorylation, resulting in inhibition of…”
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Adlowitz, D. G., Barnard, J., Biear, J. N., Cistrone, C., Owen, T., Wang, W., Palanichamy, A., Ezealah, E., Campbell, D., Wei, C., et al. (2015) · PLoS ONE · doi:10.1371/journal.pone.0128269 · Cited by 137 · see citing works
High TNF-α levels in resting B cells negatively correlate with their response
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Bagnara, D., Squillario, M., Kipling, D., Mora, T., Walczak, A. M., Silva, L. D., Weller, S., Dunn‐Walters, D. K., Weill, J., & Reynaud, C. (2015) · The Journal of Immunology · doi:10.4049/jimmunol.1500753 · Cited by 99 · see citing works
mTOR, linking metabolism and immunity
Xu, X., Ye, L., Araki, K., & Ahmed, R. (2012) · Seminars in Immunology · doi:10.1016/j.smim.2012.12.005 · Cited by 96 · see citing works
Association between LTA, TNF and AGER Polymorphisms and Late Diabetic Complications
Lindholm, E., Bakhtadze, E., Cilio, C., Agardh, E., Groop, L., & Agardh, C. (2008) · PLoS ONE · doi:10.1371/journal.pone.0002546 · Cited by 92 · see citing works
Hepatitis C viraemia reversibly maintains subset of antigen‐specific T‐bet+ tissue‐like memory B cells
Chang, L., Li, Y., & Kaplan, D. E. (2016) · Journal of Viral Hepatitis · doi:10.1111/jvh.12659 · Cited by 92 · see citing works
Tumor necrosis factor-a, biologic agents and cardiovascular risk
Sarzi‐Puttini, P., Atzeni, F., Doria, A., Iaccarino, L., & Turiel, M. (2005) · Lupus · doi:10.1191/0961203305lu2220oa · Cited by 69 · see citing works
Metabolism and autophagy in the immune system: immunometabolism comes of age
Rathmell, J. C. (2012) · Immunological Reviews · doi:10.1111/j.1600-065x.2012.01158.x · Cited by 68 · see citing works
Aging effects on T-bet expression in human B cell subsets
Frasca, D., Diaz, A., Romero, M., D’Eramo, F., & Blomberg, B. B. (2017) · Cellular Immunology · doi:10.1016/j.cellimm.2017.04.007 · Cited by 63 · see citing works
Self-citation
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Alley, D. E., Crimmins, E. M., Bandeen‐Roche, K., Guralnik, J. M., & Ferrucci, L. (2007) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.2007.01390.x · Cited by 61 · see citing works
Remodelling of biological parameters during human ageing: evidence for complex regulation in longevity and in type 2 diabetes
Spazzafumo, L., Olivieri, F., Abbatecola, A. M., Castellani, G., Monti, D., Lisa, R., Galeazzi, R., Sirolla, C., Testa, R., Ostan, R., et al. (2011) · AGE · doi:10.1007/s11357-011-9348-8 · Cited by 56 · see citing works
Paradoxical aging in HIV: immune senescence of B Cells is most prominent in young age
Rinaldi, S., Pallikkuth, S., George, V. K., de Armas, L. R., Pahwa, R., Sanchez, C. M., Pallin, M., Pan, L., Cotugno, N., Dickinson, G. M., et al. (2017) · Aging · doi:10.18632/aging.101229 · Cited by 55 · see citing works
Trafficking phenotype and production of granzyme B by double negative B cells (IgG+IgD−CD27−) in the elderly
Bulati, M., Buffa, S., Martorana, A., Candore, G., Lio, D., Caruso, C., & Colonna‐Romano, G. (2014) · Experimental Gerontology · doi:10.1016/j.exger.2013.12.011 · Cited by 50 · see citing works
Double negative (CD19+IgG+IgD−CD27−) B lymphocytes: A new insight from telomerase in healthy elderly, in centenarian offspring and in Alzheimer's disease patients
Martorana, A., Balistreri, C. R., Bulati, M., Buffa, S., Azzarello, D. M., Camarda, C., Monastero, R., Caruso, C., & Colonna‐Romano, G. (2014) · Immunology Letters · doi:10.1016/j.imlet.2014.06.003 · Cited by 47 · see citing works
Systemic and cellular consequences of macrophage control of iron metabolism
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Isaacs, J. D. (2009) · Expert Opinion on Biological Therapy · doi:10.1517/14712590903379494 · Cited by 41 · see citing works
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Verbist, K., Wang, R., & Green, D. R. (2012) · Seminars in Immunology · doi:10.1016/j.smim.2012.12.006 · Cited by 40 · see citing works
Maturational characteristics of HIV-specific antibodies in viremic individuals
Meffre, E., Louie, A., Bannock, J. M., Kim, L. J. Y., Ho, J., Frear, C. C., Kardava, L., Wang, W., Buckner, C. M., Wang, Y., et al. (2016) · JCI Insight · doi:10.1172/jci.insight.84610 · Cited by 39 · see citing works
Sensing the immune microenvironment to coordinate T cell metabolism, differentiation & function
Heikamp, E., & Powell, J. D. (2012) · Seminars in Immunology · doi:10.1016/j.smim.2012.12.003 · Cited by 21 · see citing works

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Yildiz, O., Schroth, J., Tree, T., Turner, M. R., Shaw, P. J., Henson, S. M., & Malaspina, A. (2023) · Neurology Neuroimmunology & Neuroinflammation · doi:10.1212/nxi.0000000000200042 · Cited by 39 · see citing works
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Mohapatra, L., Mishra, D. K., Tripathi, A. S., & Parida, S. K. (2023) · International Immunopharmacology · doi:10.1016/j.intimp.2023.110521 · Cited by 36 · see citing works
Intrinsic and extrinsic contributors to defective CD8+ T cell responses with aging
Jergović, M., Smithey, M. J., & Nikolich‐Žugich, J. (2018) · Experimental Gerontology · doi:10.1016/j.exger.2018.01.011 · Cited by 33 · see citing works
Metabolic pathways in immune senescence and inflammaging: Novel therapeutic strategy for chronic inflammatory lung diseases. An EAACI position paper from the Task Force for Immunopharmacology
Roth‐Walter, F., Adcock, I. M., Benito‐Villalvilla, C., Bianchini, R., Bjermer, L. H., Caramori, G., Cari, L., Chung, K. F., Diamant, Z., Eguíluz‐Gracia, I., et al. (2023) · Allergy · doi:10.1111/all.15977 · Cited by 31 · see citing works
Age-Related Alterations in Immune Function and Inflammation: Focus on Ischemic Stroke
Chen, Q., Wu, M., Tang, Q., Yan, P., & Zhu, L. (2023) · Aging and Disease · doi:10.14336/ad.2023.0721-1 · Cited by 33 · see citing works
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 · see citing works
Potential of Mesenchymal Stem Cells in the Rejuvenation of the Aging Immune System
Yeo, G. E. C., Ng, M. H., Nordin, F., & Law, J. X. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22115749 · Cited by 27 · see citing works
Targeting senescent cells for vascular aging and related diseases
Ding, Y.-N., Wang, H.-Y., Chen, H., & Liu, D. (2021) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2021.08.009 · Cited by 29 · see citing works
Circulating biomarkers of inflammaging as potential predictors of COVID-19 severe outcomes
Sabbatinelli, J., Matacchione, G., Giuliani, A., Ramini, D., Rippo, M. R., Procopio, A. D., Bonafè, M., & Olivieri, F. (2022) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2022.111667 · Cited by 27 · see citing works
Dysregulation of leukocyte trafficking in ageing: Causal factors and possible corrective therapies
Hopkin, S. J., Lord, J. M., & Chimen, M. (2020) · Pharmacological Research · doi:10.1016/j.phrs.2020.105323 · Cited by 25 · see citing works
B Lymphocytes in Parkinson’s Disease
Scott, K. M. (2022) · Journal of Parkinson s Disease · doi:10.3233/jpd-223418 · Cited by 25 · see citing works
Unbiased Screening Identifies Functional Differences in NK Cells After Early Life Psychosocial Stress
Fernandes, S. B., Patil, N. D., Mériaux, S. B., Thérésine, M., Muller, C. P., Leenen, F. A. D., Elwenspoek, M. M. C., Zimmer, J., & Turner, J. D. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.674532 · Cited by 22 · see citing works
Changes in T and B cell subsets in end stage renal disease patients before and after kidney transplantation
Wang, L., Rondaan, C., de Joode, A. A. E., Raveling‐Eelsing, E., Bos, N. A., & Westra, J. (2021) · Immunity & Ageing · doi:10.1186/s12979-021-00254-9 · Cited by 22 · see citing works
Patho-Physiology of Aging and Immune-Senescence: Possible Correlates With Comorbidity and Mortality in Middle-Aged and Old COVID-19 Patients
Farheen, S., Agrawal, S., Zubair, S., Agrawal, A., Jamal, F., Altaf, I., Anwar, A. K., Umair, S. M., & Owais, M. (2021) · Frontiers in Aging · doi:10.3389/fragi.2021.748591 · Cited by 23 · see citing works
Cells in Atherosclerosis: Focus on Cellular Senescence from Basic Science to Clinical Practice
Molnár, A., Pásztor, D. T., Tarcza, Z., & Merkely, B. P. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms242417129 · Cited by 21 · see citing works
Decoding senescence of aging single cells at the nexus of biomaterials, microfluidics, and spatial omics
Venkataraman, A., Kordic, I., Li, J., Zhang, N. Y., Bharadwaj, N. S., Fang, Z., Das, S., & Coskun, A. F. (2024) · npj Aging · doi:10.1038/s41514-024-00178-w · Cited by 22 · see citing works
The Immune System and Cellular Senescence: A Complex Interplay in Aging and Disease
Ayoub, M., Jaoude, C. A., Ayoub, M., Hamadé, A., & Rima, M. (2025) · Immunology · doi:10.1111/imm.70036 · Cited by 22 · see citing works
On Deep Landscape Exploration of COVID-19 Patients Cells and Severity Markers
Vázquez-Jiménez, A., de León, U. A.-P., Matadamas-Guzman, M. L., Muciño-Olmos, E. A., Martínez-López, Y. E., Escobedo-Tapia, T., & Reséndis-Antonio, O. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.705646 · Cited by 18 · see citing works
Effects of Morbid Obesity and Metabolic Syndrome on the Composition of Circulating Immune Subsets
Wijngaarden, L. H., van der Harst, E., Klaassen, R. A., Dunkelgrün, M., Kuijper, T. M., Klepper, M., Ambagtsheer, G., IJzermans, J. N. M., de Bruin, R. W. F., & Litjens, N. H. R. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.675018 · Cited by 17 · see citing works
Immune Diseases Associated with Aging: Molecular Mechanisms and Treatment Strategies
Kim, M. E., & Lee, J. S. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms242115584 · Cited by 17 · see citing works
Immunosenescence and Inflammaging in COVID-19
Asghari, F., Asghary, A., Zolbanin, N. M., Faraji, F., & Jafari, R. (2023) · Viral Immunology · doi:10.1089/vim.2023.0045 · Cited by 16 · see citing works
Senotherapy for chronic lung disease
Barnes, P. J. (2025) · Pharmacological Reviews · doi:10.1016/j.pharmr.2025.100069 · Cited by 17 · see citing works
Immunological Theory of Aging
Fülöp, T., Witkowski, J. M., Larbi, A., Cohen, A. A., Frost, E. H., & Pawelec, G. (2019) · Springer eBooks · doi:10.1007/978-3-319-69892-2_66-1 · Cited by 15 · see citing works
Spontaneous and induced adaptive immune responses in Alzheimer’s disease: new insights into old observations
Chen, Y., & Colonna, M. (2022) · Current Opinion in Immunology · doi:10.1016/j.coi.2022.102233 · Cited by 13 · see citing works
Cellular senescence and cell therapy in cardiovascular diseases
Chang, D., Wang, J., Zhu, S., Shentu, Y., Wang, Y., Zhu, P., & Ōno, M. (2025) · Stem Cell Research & Therapy · doi:10.1186/s13287-025-04731-6 · Cited by 13 · see citing works
Should we Try to Alleviate Immunosenescence and Inflammaging - Why, How and to What Extent?
Witkowski, J. M., Bryl, E., & Fülöp, T. (2019) · Current Pharmaceutical Design · doi:10.2174/1381612825666191111153016 · Cited by 11 · see citing works
Anticyclic Citrullinated Peptide Antibodies 3.1 and Anti-CCP-IgA Are Associated with Increasing Age in Individuals Without Rheumatoid Arthritis
Berens, H. M., Polinski, K. J., Mikuls, T. R., Khatter, S., August, J., Visser, A., Mähler, M., Weisman, M. H., O’Dell, J. R., Keating, R. M., et al. (2019) · The Journal of Rheumatology · doi:10.3899/jrheum.180897 · Cited by 11 · see citing works
Single-cell analysis of human peripheral blood reveals high immune response activity in successful ageing individuals
Wang, Y., Zhang, Y., Gong, G., Liu, Q., Li, L., Zhang, M., Shen, S., Wang, R., Wu, J., & Xu, W. (2024) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2024.112011 · Cited by 10 · see citing works
T‐cell senescence was correlated with early atherosclerosis in patients with systemic lupus erythematosus
Pratama, M. Z., Wahono, C. S., Aslam, A. B. N., Chilmi, S., Sari, V. P., Abdurrohman, A., Sulistiyowati, I., Aditya, A., Johono, M. F., & Robert (2024) · International Journal of Rheumatic Diseases · doi:10.1111/1756-185x.15339 · Cited by 9 · see citing works
Examining B-cell dynamics and responsiveness in different inflammatory milieus using an agent-based model
Shin, B., An, G. C., & Cockrell, R. C. (2024) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1011776 · Cited by 8 · see citing works
Aging and immunity: the age-old tangoPreprint
Fernández-Maestre, I., Harris, A. S., & Amor, C. (2025) · Genes & Development · doi:10.1101/gad.352644.125 · Cited by 8 · see citing works
Immunoglobulins: Mechanistic Approaches in Moderation of Various Inflammatory and Anti-inflammatory Pathways
Pasricha, C., Bansal, N., Kaur, R., Kumari, P., Jangra, S., & Singh, R. J. (2024) · Current Pharmaceutical Biotechnology · doi:10.2174/0113892010310906240725072426 · Cited by 7 · see citing works
Demographic and Clinical Factors Associated with Reactivity of Anti-SARS-CoV-2 Antibodies in Serbian Convalescent Plasma Donors
Grujić, J., Bujandrić, N., Budakov-Obradović, Z., Dolinaj, V., Bogdan, D., Savić, N., Cabezas‐Cruz, A., Mijatović, D., Simin, V., Anđelić, N., et al. (2021) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph19010042 · Cited by 7 · see citing works
Bariatric surgery reverses morbid obesity-induced changes in the composition of circulating immune cells—a prospective cohort study
Taselaar, A. E., Wijngaarden, L. H., Klaassen, R. A., van der Harst, E., Dunkelgrün, M., Kuijper, T. M., Ambagtsheer, G., Hendriks, T., de Bruin, R. W. F., & Litjens, N. H. R. (2025) · Surgery for Obesity and Related Diseases · doi:10.1016/j.soard.2024.12.025 · Cited by 6 · see citing works
Aberrations in peripheral B lymphocytes and B lymphocyte subsets levels in Parkinson disease: a systematic review
Ma, H., Wang, Z., Yu, M., Zhai, Y., & Yan, J. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1526095 · Cited by 4 · see citing works
Immunological Theory of Aging
Fülöp, T., Witkowski, J. M., Larbi, A., Cohen, A. A., Frost, E. H., & Pawelec, G. (2021) · Springer eBooks · doi:10.1007/978-3-030-22009-9_66 · Cited by 4 · see citing works
B Cell Levels in Centenarians, Semi-Supercentenarians, and Supercentenarians: Descriptive Analysis by Age, Sex, Cytomegalovirus Status, and Interleukin-6
Bertolazzi, G., Calabrò, A., Accardi, G., Aiello, A., Caruso, C., Corsale, A. M., Simone, M. D., Meraviglia, S., & Candore, G. (2026) · Journal of Ageing and Longevity · doi:10.3390/jal6010009 · Cited by 3 · see citing works
Relationship between cytomegalovirus antibody levels and cognitive performance is dependent on age and genetic risk
Vacher, M. A., Lee, S., Price, P., Ha, P., Waters, S., & Laws, S. M. (2025) · BMC Neurology · doi:10.1186/s12883-025-04279-1 · Cited by 2 · see citing works
Differential metabolic pathways underlie THC- and CBD-mediated inhibition of B-cell activation in both young and aged mice
Yekhtin, Z., Petukhov, D., Khuja, I., Kogan, N. M., Or, R., & Almogi‐Hazan, O. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1605474 · Cited by 2 · see citing works
Gearing up for the Future: Mitigating Dysregulated Inflammation in Aging and Facets of Obesity
Xu, W., & Larbi, A. (2020) · Immunometabolism · doi:10.20900/immunometab20210002 · Cited by 2 · see citing works
Reduced immune response to SARS-CoV-2 infection in the elderly after 6 months
Luo, Q., Song, Q., Li, Y., Zong, K., Liu, T., He, J., Mei, G.-Y., Du, H., Xia, Z., Liu, M., et al. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1596065 · Cited by 1 · see citing works
The impact of growth hormone (GH) on immunosenescence: exploring the role of B and T cells
Bashir, B., van Hoolwerff, M., Benencia, F., Duran‐Ortiz, S., List, E. O., Kopchick, J. J., & Berryman, D. E. (2026) · Pituitary · doi:10.1007/s11102-025-01632-y · Cited by 1 · see citing works
Immunology of Ageing
Pawelec, G., & Müller, L. (2024) · Springer eBooks · doi:10.1007/978-3-030-74720-6_104 · Cited by 1 · see citing works
Immune Responses in the Elderly
Vadasz, Z., & Toubi, E. (2020) · Springer eBooks · doi:10.1007/978-3-030-44234-7_4 · Cited by 1 · see citing works
Immunological Changes
Fülöp, T., Larbi, A., Khalil, A., Hirokawa, K., Cohen, A. A., & Witkowski, J. M. (2022) · Lessons from the ICU · doi:10.1007/978-3-030-94133-8_6 · Cited by 1 · see citing works
Ageing and vaccination in transplant patients
Wang, L. (2021) · doi:10.33612/diss.160954435
Immunology of Ageing
Pawelec, G., & Müller, L. (2021) · Springer eBooks · doi:10.1007/978-3-030-01782-8_104-1
Визначення показників ризику виникнення дифтерії на підставі дослідження антидифтерійного імунітету у населення Дніпропетровщини
Будаєва, І. В., Ревенко, Г. О., Маврутенков, В. В., Shtepa, O., Rezvykh, V., Kuzmenko, O. V., & Belova, I. P. (2021) · ACTUAL INFECTOLOGY · doi:10.22141/2312-413x.9.5-6.2021.246692
Faculty Opinions recommendation of CD27- IgD- B cell memory subset associates with inflammation and frailty in elderly individuals but only in males.
Pawelec, G. (2019) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.736457880.793564634
Senescent white blood cells in colorectal carcinoma patients
Thin, K. A. (2022) · doi:10.58837/chula.the.2022.25
Molecular Mechanisms of Cellular Senescence and Immuno-Senescence: Insights from Model Organisms and Emerging Pathways
Molla, A. (2025) · American Journal of Biomedical and Life Sciences · doi:10.11648/j.ajbls.20251305.12
Additional file 1 of Changes in T and B cell subsets in end stage renal disease patients before and after kidney transplantation
Wang, L., Rondaan, C., de Joode, A. A. E., Raveling‐Eelsing, E., Bos, N. A., & Westra, J. (2021) · Figshare · doi:10.6084/m9.figshare.16960328
Évaluation de la sénescence endothéliale et leucocytaire dans le choc septique
Merdji, H. (2021) · doi:10.70675/cbfec802z6c0dz4e06z9276zd4a44c11c814
Immunoglobulin G in aging and cancer
Bu, M., Li, Z., Jones, E., Lubaba, U., Liu, X., & Li, H. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1854902
The cross-talk between T and B lymphocytes and the oral microbiome in health and disease: a narrative review
Ordyniec-Kwaśnica, I., Słomiński, B., Lampkowski, M., Kudra, A., & Muszyński, D. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1862609

Immunesenescence and Compromised Removal of Senescent Cells: Implications for Health in Old Age
Hazeldine, J., & Lord, J. M. (2021) · Healthy ageing and longevity · doi:10.1007/978-3-030-87532-9_3 · Cited by 1 · see citing works
B Cell Immunosenescence
Frasca, D., Diaz, A., Romero, M., Garcia, D., & Blomberg, B. B. (2020) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-011620-034148 · Cited by 226 · see citing works
Self-citation
From lymphopoiesis to plasma cells differentiation, the age-related modifications of B cell compartment are influenced by “inflamm-ageing”
Bulati, M., Caruso, C., & Colonna‐Romano, G. (2017) · Ageing Research Reviews · doi:10.1016/j.arr.2017.04.001 · Cited by 113 · see citing works
The immunogenetics of immune senescence.
Weksler, M. E., & Schwab, R. (1992) · PubMed · Cited by 22 · see citing works
Molecular Mechanisms of Compromised B-Cell Functions During Immunosenescence.
Yang, X., ElKhal, A., Edtinger, K., Quante, M., Slegtenhorst, B. R., Rodriguez, H., Uehara, H., & Tullius, S. G. (2014) · Transplantation · doi:10.1097/00007890-201407151-01273

Authors: Frasca, D.
Affiliations: University of Miami (US)
Corresponding author: Frasca, Daniela
ORCID: Frasca, Daniela
Venue: Experimental Gerontology
Publisher: Elsevier BV
Published: 2018-07
Volume: 107
Pages: 55-58
ISSN: 0531-5565 (ISSN-L)
DOI: 10.1016/j.exger.2017.07.002
PMC: PMC5754260
OpenAlex: W2727145347
Cited by: 82
References: 49
Citations by year: 2026: 4 · 2025: 12 · 2024: 7 · 2023: 8 · 2022: 12 · 2021: 21 · 2020: 7 · 2019: 8 · 2018: 3
FWCI: 0.60
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Experimental Gerontology (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: NIH (R56 AG32576, R21 AI096446)
Topics: Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
Keywords: cellular senescence, aging, age-related diseases, antibody response, senescence-associated secretory phenotype, pro-inflammatory mediators, energy sensing, immunosenescence
MeSH terms: Aged, Aging, Antibody Formation, B-Lymphocytes, Biological Transport, Humans, Killer Cells, Natural, Cellular Senescence, Cell Proliferation

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Senescent B cells in aging and age-related diseases: Their role in the regulation of antibody responses

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