Aging Impairs Murine B Cell Differentiation and Function in Primary and Secondary Lymphoid Tissues

Overview

Journal Aging Dis

Specialty Geriatrics

Date 2012 Mar 8

PMID 22396888

Citations 16

Authors

Daniela Frasca

Bonnie B Blomberg

Affiliations

Soon will be listed here.

Abstract

Age-related changes in humoral immunity are responsible for the reduced vaccine responses observed in elderly individuals. Although aging has been shown to affect T cells, dendritic cells and macrophages and these effects significantly impact humoral responses, intrinsic alterations in B cells also occur. We here provide an overview of age-related changes in mouse B cells. In particular, we summarize data from the literature showing age-related changes in B cell differentiation in the bone marrow, in B cell marker expression and cell survival in the periphery and in the ability to make specific antibodies in both splenic and mucosal tissues. Moreover, we summarize the results from our studies showing that the ability to undergo class switch recombination, the enzyme activation-induced cytidine deaminase and the transcription factor E47 are all decreased in stimulated B cells from old mice. The defects presented in this review for aged B cells should allow the discovery of strategies for improvement of humoral immune responses in both humans and mice in the near future.

Citing Articles

Human monocyte subtype expression of neuroinflammation- and regeneration-related genes is linked to age and sex.

Tampe J, Monni E, Palma-Tortosa S, Brogardh E, Boiers C, Lindgren A PLoS One. 2024; 19(10):e0300946.

PMID: 39475881 PMC: 11524521. DOI: 10.1371/journal.pone.0300946.

Acute inflammation alters lung lymphocytes and potentiates innate-like behavior in young mouse lung CD8 T cells, resembling lung CD8 T cells from old mice.

Piergallini T, Scordo J, Allue-Guardia A, Pino P, Zhang H, Cai H J Leukoc Biol. 2023; 114(3):237-249.

PMID: 37196159 PMC: 10473256. DOI: 10.1093/jleuko/qiad060.

Myc-Interacting Zinc Finger Protein 1 (Miz-1) Is Essential to Maintain Homeostasis and Immunocompetence of the B Cell Lineage.

Piskor E, Ross J, Moroy T, Kosan C Biology (Basel). 2022; 11(4).

PMID: 35453704 PMC: 9027237. DOI: 10.3390/biology11040504.

The Dynamics of B Cell Aging in Health and Disease.

de Mol J, Kuiper J, Tsiantoulas D, Foks A Front Immunol. 2021; 12:733566.

PMID: 34675924 PMC: 8524000. DOI: 10.3389/fimmu.2021.733566.

Age and Periodontal Health - Immunological View.

Ebersole J, Dawson 3rd D, Emecen Huja P, Pandruvada S, Basu A, Nguyen L Curr Oral Health Rep. 2018; 5(4):229-241.

PMID: 30555774 PMC: 6291006. DOI: 10.1007/s40496-018-0202-2.

References

Agren L, Ekman L, Lowenadler B, Lycke N . Genetically engineered nontoxic vaccine adjuvant that combines B cell targeting with immunomodulation by cholera toxin A1 subunit. J Immunol. 1997; 158(8):3936-46. View

Cancro M, Hao Y, Scholz J, Riley R, Frasca D, Dunn-Walters D . B cells and aging: molecules and mechanisms. Trends Immunol. 2009; 30(7):313-8. PMC: 2766868. DOI: 10.1016/j.it.2009.04.005. View

Anspach J, Poulsen G, Kaattari I, Pollock R, Zwollo P . Reduction in DNA binding activity of the transcription factor Pax-5a in B lymphocytes of aged mice. J Immunol. 2001; 166(4):2617-26. DOI: 10.4049/jimmunol.166.4.2617. View

Fujihashi K, Kiyono H . Mucosal immunosenescence: new developments and vaccines to control infectious diseases. Trends Immunol. 2009; 30(7):334-43. DOI: 10.1016/j.it.2009.04.004. View

Frasca D, Landin A, Lechner S, Ryan J, Schwartz R, Riley R . Aging down-regulates the transcription factor E2A, activation-induced cytidine deaminase, and Ig class switch in human B cells. J Immunol. 2008; 180(8):5283-90. DOI: 10.4049/jimmunol.180.8.5283. View

Aspinall R, Andrew D . Thymic atrophy in the mouse is a soluble problem of the thymic environment. Vaccine. 2000; 18(16):1629-37. DOI: 10.1016/s0264-410x(99)00498-3. View

Manz R, Thiel A, Radbruch A . Lifetime of plasma cells in the bone marrow. Nature. 1997; 388(6638):133-4. DOI: 10.1038/40540. View

Lim H, Hillsamer P, Banham A, Kim C . Cutting edge: direct suppression of B cells by CD4+ CD25+ regulatory T cells. J Immunol. 2005; 175(7):4180-3. DOI: 10.4049/jimmunol.175.7.4180. View

Hagiwara Y, McGhee J, Fujihashi K, Kobayashi R, Yoshino N, Kataoka K . Protective mucosal immunity in aging is associated with functional CD4+ T cells in nasopharyngeal-associated lymphoreticular tissue. J Immunol. 2003; 170(4):1754-62. DOI: 10.4049/jimmunol.170.4.1754. View

10.

Herrero C, Sebastian C, Marques L, Comalada M, Xaus J, Valledor A . Immunosenescence of macrophages: reduced MHC class II gene expression. Exp Gerontol. 2002; 37(2-3):389-94. DOI: 10.1016/s0531-5565(01)00205-4. View

11.

Miller J, Allman D . The decline in B lymphopoiesis in aged mice reflects loss of very early B-lineage precursors. J Immunol. 2003; 171(5):2326-30. DOI: 10.4049/jimmunol.171.5.2326. View

12.

Biagi E, Candela M, Franceschi C, Brigidi P . The aging gut microbiota: new perspectives. Ageing Res Rev. 2011; 10(4):428-9. DOI: 10.1016/j.arr.2011.03.004. View

13.

Biagi E, Nylund L, Candela M, Ostan R, Bucci L, Pini E . Through ageing, and beyond: gut microbiota and inflammatory status in seniors and centenarians. PLoS One. 2010; 5(5):e10667. PMC: 2871786. DOI: 10.1371/journal.pone.0010667. View

14.

Stoecklin G, Anderson P . Posttranscriptional mechanisms regulating the inflammatory response. Adv Immunol. 2006; 89:1-37. DOI: 10.1016/S0065-2776(05)89001-7. View

15.

Guerrettaz L, Johnson S, Cambier J . Acquired hematopoietic stem cell defects determine B-cell repertoire changes associated with aging. Proc Natl Acad Sci U S A. 2008; 105(33):11898-902. PMC: 2515225. DOI: 10.1073/pnas.0805498105. View

16.

Miller C, Kelsoe G . Ig VH hypermutation is absent in the germinal centers of aged mice. J Immunol. 1995; 155(7):3377-84. View

17.

Zhao D, Thornton A, DiPaolo R, Shevach E . Activated CD4+CD25+ T cells selectively kill B lymphocytes. Blood. 2006; 107(10):3925-32. PMC: 1895290. DOI: 10.1182/blood-2005-11-4502. View

18.

Brooks S, Connolly J, Rigby W . The role of mRNA turnover in the regulation of tristetraprolin expression: evidence for an extracellular signal-regulated kinase-specific, AU-rich element-dependent, autoregulatory pathway. J Immunol. 2004; 172(12):7263-71. DOI: 10.4049/jimmunol.172.12.7263. View

19.

Johnson S, Rozzo S, Cambier J . Aging-dependent exclusion of antigen-inexperienced cells from the peripheral B cell repertoire. J Immunol. 2002; 168(10):5014-23. DOI: 10.4049/jimmunol.168.10.5014. View

20.

Sansoni P, Vescovini R, Fagnoni F, Biasini C, Zanni F, Zanlari L . The immune system in extreme longevity. Exp Gerontol. 2007; 43(2):61-5. DOI: 10.1016/j.exger.2007.06.008. View