Cited by 206T-cell and B-cell ImmunologyImmunodeficiency and Autoimmune DisordersLymphoma Diagnosis and Treatment

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The Effect of Age on the B-Cell Repertoire

Weksler, Marc E., Szabo, Paul·2000·Journal of Clinical Immunology

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Abstract

The antibody repertoire changes with age. This change reflects, in part, the age-associated impairment in the production of a diverse population of naive B cells in the bone marrow and, in part, by the decreased diversification of B cells in the germinal center where affinity maturation and isotype switching takes place. B cell number is strictly regulated and despite the decreased output of B cells by the bone marrow does not decline during aging. Self-renewal of peripheral B cells is sufficient to assure the stability of peripheral B cell number. However, when B cell production is stressed as, for example, following drug-induced lymphopenia, the rate of recovery of B cell number as well as of B cell diversity is compromised in old compared to young mice. Finally, aging is associated with the appearance of B cell clonal expansions which not only limit the diversity of the B cell repertoire but very likely give rise to monoclonal serum immunoglobulins and B cell neoplasms.

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Douek, D. C., McFarland, R. D., Keiser, P. H., Gage, E. A., Massey, J. M., Haynes, B. F., Polis, M. A., Haase, A. T., Feinberg, M. B., Sullivan#, J. L., et al. (1998) · Nature · doi:10.1038/25374 · Cited by 1,893
The Protective Efficacy of Polyvalent Pneumococcal Polysaccharide Vaccine
Shapiro, E. D., Berg, A. T., AUSTRIAN, R. C., Schroeder, D., Parcells, V., Margolis, A., Adair, R. K., & Clemens, J. D. (1991) · New England Journal of Medicine · doi:10.1056/nejm199111213252101 · Cited by 1,050
The immunology of exceptional individuals: the lesson of centenarians
Franceschi, C., Monti, D., Sansoni, P., & Cossarizza, A. (1995) · Immunology Today · doi:10.1016/0167-5699(95)80064-6 · Cited by 535
Lymphocyte Phytohemagglutinin Responsiveness, Immunoglobulins and Autoantibodies in Aging Humans
Hallgren, H. M., Buckley, C. E., Gilbertsen, V. A., & Yunis, E. J. (1973) · The Journal of Immunology · doi:10.4049/jimmunol.111.4.1101 · Cited by 282
Immunological studies of aging. II. Loss of IgG and high avidity plaque-forming cells and increased suppressor cell activity in aging mice.
Goidl, E. A., Innes, J. B., & Weksler, M. E. (1976) · The Journal of Experimental Medicine · doi:10.1084/jem.144.4.1037 · Cited by 240
Self-citation
Immunosenescence and germinal center reaction
Zheng, B. Q., Han, S., Takahashi, Y., & Kelsoe, G. H. (1997) · Immunological Reviews · doi:10.1111/j.1600-065x.1997.tb01028.x · Cited by 229
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Lam, K., & Rajewsky, K. (1999) · The Journal of Experimental Medicine · doi:10.1084/jem.190.4.471 · Cited by 223
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Stephan, R. P., Reilly, C. R., & Witte, P. L. (1998) · Blood · doi:10.1182/blood.v91.1.75 · Cited by 197
Natural and Vaccine-Related Immunity to Streptococcus pneumoniae
Musher, D. M., Chapman, A. J., Goree, A., Jónsson, S., Briles, D. E., & BAUGHN, R. E. (1986) · The Journal of Infectious Diseases · doi:10.1093/infdis/154.2.245 · Cited by 197
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Self-citation
Mature murine B and T cells transferred to SCID mice can survive indefinitely and many maintain a virgin phenotype.
Sprent, J., Schaefer, M. L., Hurd, M., Surh, C. D., & Ron, Y. (1991) · The Journal of Experimental Medicine · doi:10.1084/jem.174.3.717 · Cited by 175
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Kline, G. H., Hayden, T. A., & Klinman, N. R. (1999) · The Journal of Immunology · doi:10.4049/jimmunol.162.6.3342 · Cited by 170
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Kyle, R. A., & Rajkumar, S. V. (1999) · Hematology/Oncology Clinics of North America · doi:10.1016/s0889-8588(05)70120-9 · Cited by 167
RECIPROCAL CHANGE WITH AGE IN ANTIBODY TO EXTRINSIC AND INTRINSIC ANTIGENS
Rowley, M. J., Buchanan, H., & Mackay, I. R. (1968) · The Lancet · doi:10.1016/s0140-6736(68)92893-6 · Cited by 160
Clonal expansion within the CD4+CD57+ and CD8+CD57+ T cell subsets in chronic lymphocytic leukemia
Serrano, D., Monteiro, J., Allen, S. L., Kolitz, J. E., Schulman, P., Lichtman, S. M., Buchbinder, A., Vinciguerra, V., Chiorazzi, N., & Gregersen, P. K. (1997) · The Journal of Immunology · doi:10.4049/jimmunol.158.3.1482 · Cited by 147
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Increased frequency of rheumatoid factor precursor B lymphocytes after immunization of normal adults with tetanus toxoid.
Welch, M. J., Fong, S., Vaughan, J., & Carson, D. A. (1983) · PubMed Central · Cited by 138
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Immunoglobulin VH Gene Expression in Human Aging
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Host defense mechanisms and aging.
Schwab, R., Ca, W., & Weksler, M. E. (1989) · PubMed · Cited by 70
Self-citation
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Lower antibody response to tetanus toxoid associated with higher auto-anti-idiotypic antibody in old compared with young humans
Arreaza, E., Gibbons, J. J., Siskind, G. W., & Weksler, M. E. (1993) · Clinical & Experimental Immunology · doi:10.1111/j.1365-2249.1993.tb05965.x · Cited by 53
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Ontogeny of thymic B cells in normal mice
Nango, K.-I., Inaba, M., Inaba, K., Adachi, Y., Than, S., Ishida, T., Kumamoto, T., Uyama, M., & Ikehara, S. (1991) · Cellular Immunology · doi:10.1016/0008-8749(91)90183-c · Cited by 39
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Self-citation
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Self-citation
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Self-citation
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Doria, G., Mancini, C., Utsuyama, M., Frasca, D., & Hirokawa, K. (1997) · Mechanisms of Ageing and Development · doi:10.1016/s0047-6374(97)01871-x · Cited by 26
Differential age effect of oral administration of an antigen on antibody response: an induction of tolerance in young mice but enhancement of immune response in old mice
Wakabayashi, A., Utsuyama, M., Hosoda, T., Sato, K., & Hirokawa, K. (1999) · Mechanisms of Ageing and Development · doi:10.1016/s0047-6374(99)00036-6 · Cited by 26
Age and Antibody Production
Baumgartner, L. (1934) · The Journal of Immunology · doi:10.4049/jimmunol.27.4.407 · Cited by 24
Treatment of old mice with IL-2 corrects dysregulated IL-2 and IL-4 production
Kirman, I., Zhao, K., Tschepen, I., Szabo, P., Richter, G. W., Nguyen, H. H., & Wekslzer, M. E. (1996) · International Immunology · doi:10.1093/intimm/8.7.1009 · Cited by 20
Self-citation
Effect of age on thymic development, T cell immunity, and helper T cell function
Shen, S. S., Kim, J. S., & Weksler, M. E. (2005) · Springer eBooks · doi:10.1007/bfb0033650 · Cited by 18
Self-citation
Evaluation of presence and functional activity of potentially self-reactive T cells in aged mice
Crlsl, G. M., Tsiagbe, V. K., Russo, C., Basch, R. S., & Thorbecke, G. J. (1996) · International Immunology · doi:10.1093/intimm/8.3.387 · Cited by 17
Old mice recover the ability to produce IgG and high-avidity antibody following irradiation with partial bone marrow shielding.
Tsuda, T., Kim, Y. T., Siskind, G. W., & Weksler, M. E. (1988) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.85.4.1169 · Cited by 16
Self-citation
Ontogeny of B lymphocyte function VIII. Failure of thymus cells from aged donors to induce the functional maturation of B lymphocytes from immature donors
Szewczuk, M. R., DeKruyff, R. H., Goidl, E. A., Weksler, M. E., & Siskind, G. W. (1980) · European Journal of Immunology · doi:10.1002/eji.1830101206 · Cited by 15
Self-citation
Activation of the Recombination Activating Gene 1 (RAG-1) Transcript in Bone Marrow of Senescent C57BL/6 Mice by Recombinant Interleukin-7
Ben‐Yehuda, A., Wirtheim, E., Abdul-Hai, A., Or, R., Slavin, S., Babaey, S., & Friedman, G. (1999) · The Journals of Gerontology Series A · doi:10.1093/gerona/54.4.b143 · Cited by 11

Research works printed but not linked: 4

Thomsen O, Kettel K: Die starke der menchlichen Isoagglutinine und entsperchenden Blutkorperchenrezeptoren in verchiende Lebensaltern, Z. Immunitatsforsch 63:67, 1929.
Goidl EA, Stashak PW, Martin-McEvoy SSJ, Hiernaux JR: Age related changes in serum immunoglobulin isotypes and isotype subclass levels among standard long-lived and autoimmune and immunodeficient strains of mice: Serum Ig increases with age. Aging Immunol Infect Dis 1:227, 1989.
Rowley MJ, Buchanan H, Mackay IR, Mackay IR: Reciprocal change with age in antibody to extrinsic and intrinsic antigens. Lancet 2:24-26, 1968. · DOI
Lee JW, Jin F, Weksler ME: The nature and significance of age-associated autoimmunity. In The Molecular Pathology of Autoimmune Diseases, 2nd ed AN Theofilopoulos, C Bona (eds) (in press).

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Weiskopf, D., Weinberger, B., & Grubeck-Loebenstein, B. (2009) · Transplant International · doi:10.1111/j.1432-2277.2009.00927.x · Cited by 908
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Gruver, A., Hudson, L., & Sempowski, G. (2007) · The Journal of Pathology · doi:10.1002/path.2104 · Cited by 834
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Siegrist, C.-A., & Aspinall, R. (2009) · Nature Reviews Immunology · doi:10.1038/nri2508 · Cited by 659
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See all 206

Authors: Weksler, M. E., & Szabo, P.
Affiliations: Cornell University (US)
Venue: Journal of Clinical Immunology
Publisher: Springer Science and Business Media LLC
Published: 2000-07
Volume: 20
Issue: 4
Pages: 240-249
ISSN: 0271-9142 (ISSN-L)
1573-2592
DOI: 10.1023/a:1006659401385
OpenAlex: W1512900561
Cited by: 205
References: 45
Citations by year: 2026: 6 · 2025: 4 · 2024: 3 · 2023: 6 · 2022: 2 · 2021: 7 · 2020: 2 · 2019: 9 · 2018: 4 · 2017: 14 · 2016: 6 · 2015: 6 · 2014: 9 · 2013: 11 · 2012: 15
FWCI: 0.64
Type: journal article
Language: en
Open access: closed
Licence: www.springernature.com/gp/researchers/text-and-data-mining (tdm)
www.springernature.com/gp/researchers/text-and-data-mining (vor)
Locations: Journal of Clinical Immunology (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (5p01ag014669-03)
National Institute on Aging (AG-14669)
Topics: Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Life Sciences › Immunology and Microbiology › Immunology › Immunodeficiency and Autoimmune Disorders
Health Sciences › Medicine › Pathology and Forensic Medicine › Lymphoma Diagnosis and Treatment
Keywords: B cell receptor repertoire, aging, naive B cells, bone marrow, germinal center, affinity maturation, class switch recombination, lymphopenia, B cell clonal expansion, M protein, B-cell malignancies, antibody diversity
MeSH terms: Adjuvants, Immunologic, Aged, Aging, Animals, Antibodies, Anti-Idiotypic, Antibody Formation, Antigens, Bacterial, Autoantibodies, Bone Marrow, Cell Division, Clone Cells, Disease Susceptibility, Hematopoiesis, Humans, Lymphopenia, Lymphoproliferative Disorders, Gene Rearrangement, B-Lymphocyte, Autoimmunity, B-Lymphocyte Subsets, Mice, SCID, Lymphocyte Count, Germinal Center, Mice

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The Effect of Age on the B-Cell Repertoire

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