B cell immunosenescence in the elderly and in centenarians.

The elderly suffer from an increased susceptibility to infectious disease and cancer. Aging of the immune system contributes to this state of affairs due to immunosenescence. Because repeated intermittent or chronic antigen exposure may lead to lymphocyte clonal exhaustion, chronic antigenic stress plays a part in the compromised immunity of the elderly, who have accumulated a lifetime's exposure to infectious agents, autoantigens, and cancer antigens. Literature on immunosenescence has focused mainly on T cell impairment, but B cell compartment is also affected. The age-dependent B cell changes documented by the present review indicate that advanced age per se is a condition characterized by lack of B clonotypic immune response to new extracellular pathogens. In any event, data are suggesting that the loss of naive B cells could represent a hallmark of immunosenescence and could provide a biomarker possibly related to the life span of humans and potentially useful for the evaluation of anti-aging treatment. Since information on the senescence of B cells is of obvious interest, further studies are necessary to confirm these suggestions as well as to extend the number of markers used to characterize the cells.

[1]  B. Blomberg,et al.  Aging murine B cells have decreased class switch induced by anti-CD40 or BAFF , 2007, Experimental Gerontology.

[2]  C. Caruso,et al.  Inflammatory networks in ageing, age-related diseases and longevity , 2007, Mechanisms of Ageing and Development.

[3]  E. Hoster,et al.  Booster vaccination in the elderly: their success depends on the vaccine type applied earlier in life as well as on pre-vaccination antibody titers. , 2006, Vaccine.

[4]  C. Franceschi,et al.  A Study of Serum Immunoglobulin Levels in Elderly Persons That Provides New Insights into B Cell Immunosenescence , 2006, Annals of the New York Academy of Sciences.

[5]  C. Caruso,et al.  Biology of longevity: role of the innate immune system. , 2006, Rejuvenation research.

[6]  C. Caruso,et al.  Memory B cell subpopulations in the aged. , 2006, Rejuvenation research.

[7]  Daniel Rodríguez‐Pinto B cells as antigen presenting cells. , 2005, Cellular immunology.

[8]  B. Blomberg,et al.  Humoral immune response and B-cell functions including immunoglobulin class switch are downregulated in aged mice and humans. , 2005, Seminars in immunology.

[9]  K. Agematsu,et al.  Regulation of Aged Humoral Immune Defense against Pneumococcal Bacteria by IgM Memory B Cell , 2005, The Journal of Immunology.

[10]  G. Pawelec,et al.  Human immunosenescence: is it infectious? , 2005, Immunological reviews.

[11]  Joshy Jacob,et al.  B Lymphocytes Participate in Cross-Presentation of Antigen following Gene Gun Vaccination 1 , 2005, The Journal of Immunology.

[12]  S. Kashiwagi,et al.  CD27(+) (memory) B cell decrease and apoptosis-resistant CD27(-) (naive) B cell increase in aged humans: implications for age-related peripheral B cell developmental disturbances. , 2005, International immunology.

[13]  A. Cappione,et al.  Rituximab improves peripheral B cell abnormalities in human systemic lupus erythematosus. , 2004, Arthritis and rheumatism.

[14]  C. Caruso,et al.  Immunity & Ageing: a new journal looking at ageing from an immunological point of view , 2004, Immunity & Ageing.

[15]  D. Mari,et al.  Anti-beta 2 glycoprotein I antibodies in centenarians , 2004, Experimental Gerontology.

[16]  G. Pawelec,et al.  Is immunosenescence infectious? , 2004, Trends in immunology.

[17]  Andreas Radbruch,et al.  Plasma Cell Survival Is Mediated by Synergistic Effects of Cytokines and Adhesion-Dependent Signals1 , 2003, The Journal of Immunology.

[18]  H. Ochs,et al.  Functional analysis of human memory B-cell subpopulations: IgD+CD27+ B cells are crucial in secondary immune response by producing high affinity IgM. , 2003, Clinical immunology.

[19]  C. Caruso,et al.  B cells in the aged: CD27, CD5, and CD40 expression , 2003, Mechanisms of Ageing and Development.

[20]  G. Kelsoe,et al.  Enhanced Differentiation of Splenic Plasma Cells but Diminished Long-Lived High-Affinity Bone Marrow Plasma Cells in Aged Mice 1 , 2003, The Journal of Immunology.

[21]  Antonio Lanzavecchia,et al.  Maintenance of Serological Memory by Polyclonal Activation of Human Memory B Cells , 2002, Science.

[22]  J. Tew,et al.  Age‐related depression of FDC accessory functions and CD21 ligand‐mediated repair of co‐stimulation , 2002, European journal of immunology.

[23]  G. Pawelec,et al.  Is human immunosenescence clinically relevant? Looking for 'immunological risk phenotypes'. , 2002, Trends in immunology.

[24]  C. Franceschi,et al.  T cells and aging, January 2002 update. , 2002, Frontiers in bioscience : a journal and virtual library.

[25]  K. Rajewsky,et al.  Homeostasis of Peripheral B Cells in the Absence of B Cell Influx from the Bone Marrow , 2001, The Journal of experimental medicine.

[26]  Andreas Radbruch,et al.  Inflamed kidneys of NZB / W mice are a major site for the homeostasis of plasma cells , 2001, European journal of immunology.

[27]  L. Ginaldi,et al.  Immunosenescence and infectious diseases. , 2001, Microbes and infection.

[28]  K. Rajewsky,et al.  Memory B-cell persistence is independent of persisting immunizing antigen , 2000, Nature.

[29]  R. Effros,et al.  Ageing of lymphocytes and lymphocytes in the aged. , 2000, Immunology today.

[30]  P. Szabo,et al.  The Effect of Age on the B-Cell Repertoire , 2000, Journal of Clinical Immunology.

[31]  C. Franceschi,et al.  Inflamm‐aging: An Evolutionary Perspective on Immunosenescence , 2000 .

[32]  A. Komiyama,et al.  CD27: a memory B-cell marker. , 2000, Immunology today.

[33]  C. Franceschi,et al.  Shortage of circulating naive CD8(+) T cells provides new insights on immunodeficiency in aging. , 2000, Blood.

[34]  M. Weksler,et al.  Changes in the B-cell repertoire with age. , 2000, Vaccine.

[35]  C. Franceschi,et al.  Human immunosenescence: the prevailing of innate immunity, the failing of clonotypic immunity, and the filling of immunological space. , 2000, Vaccine.

[36]  N. Klinman,et al.  B cell maintenance in aged mice reflects both increased B cell longevity and decreased B cell generation. , 1999, Journal of immunology.

[37]  K. Rajewsky,et al.  Human Immunoglobulin (Ig)M+IgD+ Peripheral Blood B Cells Expressing the CD27 Cell Surface Antigen Carry Somatically Mutated Variable Region Genes: CD27 as a General Marker for Somatically Mutated (Memory) B Cells , 1998, The Journal of experimental medicine.

[38]  Andreas Radbruch,et al.  Survival of long-lived plasma cells is independent of antigen. , 1998, International immunology.

[39]  C. Caruso,et al.  Interleukin-12 release by mitogen-stimulated mononuclear cells in the elderly , 1998, Mechanisms of Ageing and Development.

[40]  G. Kelsoe,et al.  Immunosenescence and germinal center reaction , 1997, Immunological reviews.

[41]  C. Franceschi,et al.  Cytometric analysis of immunosenescence. , 1997, Cytometry.

[42]  C. Caruso,et al.  Prevalence of organ-specific and non organ-specific autoantibodies in healthy centenarians , 1997, Mechanisms of Ageing and Development.

[43]  Richard A. Miller The Aging Immune System: Primer and Prospectus , 1996, Science.

[44]  B. Johansson,et al.  Age-related changes in immune parameters in a very old population of Swedish people: A longitudinal study , 1994, Experimental Gerontology.

[45]  C. Franceschi,et al.  Thyroid and other organ-specific autoantibodies in healthy ceritenarians , 1992, The Lancet.

[46]  C. Caruso,et al.  Age- and gender-related values of lymphocyte subsets in subjects from Northern and Southern Italy. , 2002, Archives of gerontology and geriatrics. Supplement.

[47]  C. Caruso,et al.  Cytokine production pathway in the elderly , 1996, Immunologic research.

[48]  C. Franceschi,et al.  The immunology of exceptional individuals: the lesson of centenarians. , 1995, Immunology today.

[49]  C. Caruso,et al.  Blood antiphospholipid antibody levels are influenced by age, sex and HLA-B8,DR3 phenotype. , 1992, Experimental and clinical immunogenetics.