B cell maintenance and function in aging
Abstract
In this review we discuss the changes that occur in the B lymphocyte compartment of mice and humans as they progress to old age, focusing on recent advances in this important area of research. Primary areas considered include increased morbidity and mortality in the elderly following infection, and decreased responsiveness to vaccines that evoke primary humoral immune responses, as well as those that evoke responses by memory B cells generated following vaccination and natural infection earlier in life. We then consider some of the mechanisms that may underlie these observed declines in humoral immune function. This includes a discussion of alterations in B cell repertoire and subcompartment distribution, as well as defects in B lymphopoiesis, cell development and homeostasis that may contribute to these alterations, and ultimately to declining protective quality of antibodies produced in the elderly.
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With increasing age, the proportion and number of CD19+ B cells in peripheral blood decrease and the function of B cells is impaired, reflected in decreased expression of the autoimmune regulator AIRE and autoantigen genes in thymic B cells.
“With increasing age, the proportion and number of CD19+ B cells in peripheral blood decrease and the function of B cells is impaired, which is reflected in the decreased expression of the autoimmune regulator AIRE and autoantigen genes in thymic B cells [141, 142].”
From Immunosenescence: a key player in cancer development (2020) · cites this paper as [141]
Cites
Longevity, Stress Response, and Cancer in Aging Telomerase-Deficient Mice
Rudolph, K. L., Chang, S., Lee, H.-W., Blasco, M., Gottlieb, G. J., Greider, C., & DePinho, R. A. (1999) · Cell · doi:10.1016/s0092-8674(00)80580-2 · Cited by 1,349 · see citing works
Telomere dysfunction induces metabolic and mitochondrial compromise
Sahin, E., Colla, S., Liesa, M., Moslehi, J., Müller, F. L., Guo, M., Cooper, M., Kotton, D., Fabian, A. J., Walkey, C., et al. (2011) · Nature · doi:10.1038/nature09787 · Cited by 1,319 · see citing works
Cell intrinsic alterations underlie hematopoietic stem cell aging
Rossi, D. J., Bryder, D., Zahn, J. M., Ahlenius, H., Sonu, R., Wagers, A. J., & Weissman, I. L. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0503280102 · Cited by 1,152 · see citing works
Stem-cell ageing modified by the cyclin-dependent kinase inhibitor p16INK4a
Janzen, V., Forkert, R., Fleming, H. E., Saito, Y., Waring, M. T., Dombkowski, D. M., Cheng, T., DePinho, R. A., Sharpless, N. E., & Scadden, D. T. (2006) · Nature · doi:10.1038/nature05159 · Cited by 1,106 · see citing works
p16INK4a induces an age-dependent decline in islet regenerative potential
Krishnamurthy, J., Ramsey, M. R., Ligon, K. L., Torrice, C., Koh, A., Bonner-Weir, S., & Sharpless, N. E. (2006) · Nature · doi:10.1038/nature05092 · Cited by 1,003 · see citing works
Human bone marrow hematopoietic stem cells are increased in frequency and myeloid-biased with age
Pang, W. W., Price, E. A., Sahoo, D., Beerman, I., Maloney, W. J., Rossi, D. J., Schrier, S. L., & Weissman, I. L. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1116110108 · Cited by 991 · see citing works
Telomerase reactivation reverses tissue degeneration in aged telomerase-deficient mice
Jaskelioff, M., Muller, F. L., Paik, J.-H., Thomas, E., Jiang, S., Adams, A. C., Sahin, E., Kost-Alimova, M., Protopopov, A., Cadiñanos, J., et al. (2011) · Nature · doi:10.1038/nature09603 · Cited by 857 · see citing works
Gruver, A., Hudson, L., & Sempowski, G. (2007) · The Journal of Pathology · doi:10.1002/path.2104 · Cited by 834 · see citing works
Does oxidative damage to DNA increase with age?
Hamilton, M. L., Van Remmen, H., Drake, J. A., Yang, H., Guo, Z. M., Kewitt, K., Walter, C. A., & Richardson, A. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.171202698 · Cited by 768 · see citing works
Linking functional decline of telomeres, mitochondria and stem cells during ageing
Sahin, E., & DePinho, R. A. (2010) · Nature · doi:10.1038/nature08982 · Cited by 759 · see citing works
A B-cell subset uniquely responsive to innate stimuli accumulates in aged mice
Hao, Y., O'Neill, P., Naradikian, M. S., Scholz, J. L., & Cancro, M. P. (2011) · Blood · doi:10.1182/blood-2011-01-330530 · Cited by 622 · see citing works
Self-citationClonal analysis reveals multiple functional defects of aged murine hematopoietic stem cells
Dykstra, B., Olthof, S., Schreuder, J., Ritsema, M., & de Haan, G. (2011) · Journal of Experimental Medicine · doi:10.1084/jem.20111490 · Cited by 494 · see citing works
B‐cell diversity decreases in old age and is correlated with poor health status
Gibson, K. L., Wu, Y., Barnett, Y., Duggan, O., Vaughan, R., Kondeatis, E., Nilsson, B., Wikby, A., Kipling, D., & Dunn‐Walters, D. K. (2009) · Aging Cell · doi:10.1111/j.1474-9726.2008.00443.x · Cited by 433 · see citing works
Cho, R. H., Sieburg, H. B., & Muller-Sieburg, C. E. (2008) · Blood · doi:10.1182/blood-2007-11-123547 · Cited by 377 · see citing works
Frasca, D., Landin, A. M., Lechner, S. C., Ryan, J. G., Schwartz, R., Riley, R. L., & Blomberg, B. B. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.180.8.5283 · Cited by 333 · see citing works
An evolutionary perspective on the mechanisms of immunosenescence
Shanley, D. P., Aw, D., Manley, N. R., & Palmer, D. B. (2009) · Trends in Immunology · doi:10.1016/j.it.2009.05.001 · Cited by 315 · see citing works
Accumulation of DNA damage in hematopoietic stem and progenitor cells during human aging
Rübe, C. E., Fricke, A., Widmann, T. A., Fürst, T., Madry, H., Pfreundschuh, M., & Rübe, C. (2011) · PLoS ONE · doi:10.1371/journal.pone.0017487 · Cited by 307 · see citing works
Sasaki, S., Sullivan, M., Narvaez, C. F., Holmes, T. H., Furman, D., Zheng, N.-Y., Nishtala, M., Wrammert, J., Smith, K., James, J. A., et al. (2011) · Journal of Clinical Investigation · doi:10.1172/jci57834 · Cited by 300 · see citing works
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
Impaired Ability of Bone Marrow Stromal Cells to Support B-Lymphopoiesis With Age
Stephan, R. P., Reilly, C. R., & Witte, P. L. (1998) · Blood · doi:10.1182/blood.v91.1.75 · Cited by 197 · see citing works
Kline, G. H., Hayden, T. A., & Klinman, N. R. (1999) · The Journal of Immunology · doi:10.4049/jimmunol.162.6.3342 · Cited by 170 · see citing works
Expression of p16INK4a prevents cancer and promotes aging in lymphocytes
Liu, Y., Johnson, S. M., Fedoriw, Y., Rogers, A. B., Yuan, H., Krishnamurthy, J., & Sharpless, N. E. (2011) · Blood · doi:10.1182/blood-2010-09-304402 · Cited by 114 · see citing works
Immunoaging induced by hematopoietic stem cell aging
Wang, J., Geiger, H., & Rudolph, K. L. (2011) · Current Opinion in Immunology · doi:10.1016/j.coi.2011.05.004 · Cited by 107 · see citing works
B-cell depletion reactivates B lymphopoiesis in the BM and rejuvenates the B lineage in aging
Keren, Z., Naor, S., Nussbaum, S., Golan, K., Itkin, T., Sasaki, Y., Schmidt-Supprian, M., Lapidot, T., & Melamed, D. (2011) · Blood · doi:10.1182/blood-2010-09-307983 · Cited by 100 · see citing works
B cells and aging: Balancing the homeostatic equation
MILLER, J., & CANCRO, M. (2007) · Experimental Gerontology · doi:10.1016/j.exger.2007.01.010 · Cited by 67 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Inflammation and aging: signaling pathways and intervention therapies
Li, X., Li, C., Zhang, W., Wang, Y., Qian, P., & Huang, H. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01502-8 · Cited by 1,443 · see citing works
“Different from mice, as individuals age, there is a decline in the proportion and absolute number of B cells in the peripheral blood.(75,76) Especially, the aging process is associated with a rise in the proportion of late-stage exhausted memory B cells,(77) while the percentage of memory B cells that exhibit a positi…”
BackgroundThe twilight of immunity: emerging concepts in aging of the immune system
Nikolich-Žugich, J. (2018) · Nature Immunology · doi:10.1038/s41590-017-0006-x · Cited by 1,240 · see citing works
Age-dependent dysregulation of innate immunity
Shaw, A. C., Goldstein, D. R., & Montgomery, R. R. (2013) · Nature Reviews Immunology · doi:10.1038/nri3547 · Cited by 1,061 · see citing works
Understanding immunosenescence to improve responses to vaccines
Goronzy, J. J., & Weyand, C. M. (2013) · Nature Immunology · doi:10.1038/ni.2588 · Cited by 827 · see citing works
Nikolich-Zugich, J., Knox, K. S., Rios, C. T., Natt, B., Bhattacharya, D., & Fain, M. J. (2020) · GeroScience · doi:10.1007/s11357-020-00186-0 · Cited by 577 · see citing works
Immunosenescence: a key player in cancer development
Lian, J., Yue, Y., Yu, W., & Zhang, Y. (2020) · Journal of Hematology & Oncology · doi:10.1186/s13045-020-00986-z · Cited by 510 · see citing works
The aging lung: Physiology, disease, and immunity
Schneider, J. L., Rowe, J. H., Garcia-de-Alba, C., Kim, C. F., Sharpe, A. H., & Haigis, M. C. (2021) · Cell · doi:10.1016/j.cell.2021.03.005 · Cited by 500 · see citing works
Cancro, M. P. (2020) · Annual Review of Immunology · doi:10.1146/annurev-immunol-092419-031130 · Cited by 464 · see citing works
Self-citationCan physical activity ameliorate immunosenescence and thereby reduce age-related multi-morbidity?
Duggal, N. A., Niemiro, G., Harridge, S. D. R., Simpson, R. J., & Lord, J. M. (2019) · Nature Reviews Immunology · doi:10.1038/s41577-019-0177-9 · Cited by 436 · see citing works
The immune system and aging: A review
Castelo-Branco, C., & Soveral, I. (2014) · Gynecological Endocrinology · doi:10.3109/09513590.2013.852531 · Cited by 449 · see citing works
Epidemiology and Immune Pathogenesis of Viral Sepsis
Lin, G.-L., McGinley, J. P., Drysdale, S. B., & Pollard, A. J. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.02147 · Cited by 351 · see citing works
Aging of the T Cell Compartment in Mice and Humans: From No Naive Expectations to Foggy Memories
Nikolich-Žugich, J. (2014) · The Journal of Immunology · doi:10.4049/jimmunol.1401174 · Cited by 259 · see citing works
Herati, R. S., Reuter, M. A., Dolfi, D. V., Mansfield, K. D., Aung, H., Badwan, O. Z., Kurupati, R. K., Kannan, S., Ertl, H., Schmader, K. E., et al. (2014) · The Journal of Immunology · doi:10.4049/jimmunol.1302503 · Cited by 177 · see citing works
Valletta, S., Thomas, A., Meng, Y., Ren, X., Drissen, R., Sengül, H., Di Genua, C., & Nerlov, C. (2020) · Nature Communications · doi:10.1038/s41467-020-17942-7 · Cited by 122 · see citing works
Lymphocyte maintenance during healthy aging requires no substantial alterations in cellular turnover
Westera, L., van Hoeven, V., Drylewicz, J., Spierenburg, G., van Velzen, J. F., de Boer, R. J., Tesselaar, K., & Borghans, J. A. M. (2015) · Aging Cell · doi:10.1111/acel.12311 · Cited by 96 · see citing works
Plasma cell numbers decrease in bone marrow of old patients
Pritz, T., Lair, J., Ban, M., Keller, M., Weinberger, B., Krismer, M., & Grubeck‐Loebenstein, B. (2015) · European Journal of Immunology · doi:10.1002/eji.201444878 · Cited by 98 · see citing works
Aging affects B‐cell antigen receptor repertoire diversity in primary and secondary lymphoid tissues
Tabibian‐Keissar, H., Hazanov, L., Schiby, G., Rosenthal, N., Rakovsky, A., Michaeli, M., Shahaf, G. L., Pickman, Y., Rosenblatt, K., Melamed, D., et al. (2016) · European Journal of Immunology · doi:10.1002/eji.201545586 · Cited by 84 · see citing works
Inflammation and the Alteration of B-Cell Physiology in Aging
Hagen, M., & Derudder, E. (2020) · Gerontology · doi:10.1159/000501963 · Cited by 58 · see citing works
Cell signaling and the aging of B cells
Labi, V., & Derudder, E. (2020) · Experimental Gerontology · doi:10.1016/j.exger.2020.110985 · Cited by 9 · see citing works
Nutraceuticals in immunosenescence
Magrone, T., & Jirillo, E. (2015) · Anti‐ageing nutrients · doi:10.1002/9781118823408.ch5 · Cited by 4 · see citing works
- Authors
- Kogut, I., Scholz, J. L., Cancro, M. P., & Cambier, J. C.
- Affiliations
- National Jewish Health (US)
- University of Pennsylvania (US)
- Corresponding author
- Cambier, John C.
- Venue
- Seminars in Immunology
- Publisher
- Elsevier BV
- Published
- 2012-10
- Volume
- 24
- Issue
- 5
- Pages
- 342-349
- ISSN
- 1044-5323 (ISSN-L)
- OpenAlex
- W1975747345
- Semantic Scholar
- 022f6f7c2fb21c75134b864e28c82649bfa82e83
- Cited by
- 166
- References
- 25
- Citations by year
- 2026: 8 · 2025: 7 · 2024: 9 · 2023: 14 · 2022: 14 · 2021: 23 · 2020: 13 · 2019: 7 · 2018: 10 · 2017: 8 · 2016: 9 · 2015: 17 · 2014: 13 · 2013: 13 · 2012: 1
- FWCI
- 1.30
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Seminars in Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (R01AG030227, R01AG016841)
- 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 › Immunotherapy and Immune Responses
- Keywords
- B cells, aging, immunosenescence, humoral immune response, vaccine response in the elderly, memory B cells, B cell receptor repertoire, B cell development, B cell homeostasis, antibody quality
- MeSH terms
- Aging, Animals, B-Lymphocytes, Homeostasis, Humans, Vaccination, Lymphopoiesis, Cell Proliferation
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