Age-related changes in immune parameters in a very old population of Swedish people: A longitudinal study

Wikby, Anders; Johansson, Boo; Ferguson, Frederick G.; Olsson, Jadwiga

doi:10.1016/0531-5565(94)90036-1

Cited by 124 publications

(64 citation statements)

References 7 publications

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“…In particular, we confirm data from other groups showing that B cell percentages and numbers decrease with age (17)(18)(19)25), whereas the percentage of naive B cells increase with age (19,25). Moreover, we show for the first time that the subset of switch memory B cells decreases with age.…”

Section: Discussionsupporting

confidence: 77%

“…The critical role of CD40-CD40L interaction for CSR is provided by the discovery that mutations in either the CD40 or CD40L (CD154) gene cause the hyper IgM (HIGM) syndrome, HIGM3 or HIGM1, respectively, characterized by very low levels of serum IgG, IgA, and IgE, with normal or elevated IgM, associated with defective germinal center (GC) formation (16). Human B cell percentages and numbers have been shown to decrease significantly with age (17,18). It has also been shown that the percentage of IgM memory B cells, which are responsible for the response to Streptococcus pneumoniae infection, is significantly decreased whereas that of naive B cells is increased in old individuals (19).…”

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confidence: 99%

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Aging Down-Regulates the Transcription Factor E2A, Activation-Induced Cytidine Deaminase, and Ig Class Switch in Human B Cells

Frasca

Landin²,

Lechner³

et al. 2008

The Journal of Immunology

275

262

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Elderly humans have compromised humoral and cellular immune responses, which lead to reduced protection to infectious agents and to vaccines. Currently, available vaccines suboptimally protect the elderly population. The capacity to class switch the Ig H chain is critical to the effectiveness of humoral immune responses in mice and humans. We have previously shown in mice that the E2A-encoded transcription factor E47, which regulates many B cell functions, is down-regulated in old splenic B cells. This leads to a reduction in the activation-induced cytidine deaminase (AID), which is known to induce class switch recombination and Ig somatic hypermutation. The old activated murine B cells also have less AID and less switched Abs. We have extended our study here to investigate whether aging also affects Ab production and E47 and AID expression in B cells isolated from the peripheral blood of human subjects (18–86 years). Our results obtained with activated CD19+ B cells show that the expression of E47, AID, and Igγ1 circle transcripts progressively decrease with age. We also show an age-related decline in the percentage of switch memory B cells (IgG+/IgA+), an increase in that of naive B cells (IgG−/IgA−/CD27−) for most individuals, and no decrease in that of IgM memory cells in peripheral blood, consistent with our data on the decrease seen in class switch recombination in vitro. Our results provide a possible molecular mechanism for a B cell intrinsic defect in the humoral immune response with aging and suggest avenues for improvement of vaccine response in elderly humans.

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Section: Discussionsupporting

confidence: 77%

mentioning

confidence: 99%

Aging Down-Regulates the Transcription Factor E2A, Activation-Induced Cytidine Deaminase, and Ig Class Switch in Human B Cells

Frasca

Landin²,

Lechner³

et al. 2008

The Journal of Immunology

275

262

View full text Add to dashboard Cite

show abstract

“…In contrast to mouse model, in humans there is a decrease both in percentage and absolute number of total CD19 + B lymphocytes (Veneri et al, 2009;Faria et al, 2008;Frasca et al, 2008;Shi et al, 2005;Chong et al, 2005;Colonna Romano et al, 2003Breitbart et al, 2002;Huppert et al, 1998;Wikby et al, 1994;Paganelli et al, 1992). Moreover, it has been demonstrated that absolute number of B cell precursors in the bone marrow declines with age and particularly during adolescence (McKenna et al, 2001), however, B lymphopoiesis persists throughout adult life (Rossi et al, 2003).…”

Section: B Lymphocytesmentioning

confidence: 99%

B cells and immunosenescence: A focus on IgG+IgD−CD27− (DN) B cells in aged humans

Bulati¹,

Buffa²,

Candore³

et al. 2011

Ageing Research Reviews

101

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a b s t r a c tImmunosenescence contributes to the decreased ability of the elderly to control infectious diseases, which is also reflected in their generally poor response to new antigens and vaccination. It is known that the T cell branch of the immune system is impaired in the elderly mainly due to expansion of memory/effector cells that renders the immune system less able to respond to new antigens. B lymphocytes are also impaired in the elderly in terms of their response to new antigens. In this paper we review recent work on B cell immunosenescence focusing our attention on memory B cells and a subset of memory B cells (namely IgG + IgD − CD27 − ) that we have demonstrated is increased in healthy elderly.

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“…As humans age, the immune system becomes senescent (Boucher et al, 1998;Wikby, Johansson, Ferguson, & Olsson, 1994). As a consequence, older adults are less able to respond to vaccines and mount cellular immune responses, which in turn may contribute to early mortality (Ferguson, Wikby, Maxson, Olsson, & Johansson, 1995;Wayne, Rhyne, Garry, & Goodwin, 1990).…”

Section: Who Is Vulnerable To Stress-induced Immune Changes?mentioning

confidence: 99%

Psychological Stress and the Human Immune System: A Meta-Analytic Study of 30 Years of Inquiry.

Segerstrom

Miller

2004

Psychological Bulletin

2,591

1,845

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The present report meta-analyzes more than 300 empirical articles describing a relationship between psychological stress and parameters of the immune system in human participants. Acute stressors (lasting minutes) were associated with potentially adaptive upregulation of some parameters of natural immunity and downregulation of some functions of specific immunity. Brief naturalistic stressors (such as exams) tended to suppress cellular immunity while preserving humoral immunity. Chronic stressors were associated with suppression of both cellular and humoral measures. Effects of event sequences varied according to the kind of event (trauma vs. loss). Subjective reports of stress generally did not associate with immune change. In some cases, physical vulnerability as a function of age or disease also increased vulnerability to immune change during stressors.Since the dawn of time, organisms have been subject to evolutionary pressure from the environment. The ability to respond to environmental threats or stressors such as predation or natural disaster enhanced survival and therefore reproductive capacity, and physiological responses that supported such responses could be selected for. In mammals, these responses include changes that increase the delivery of oxygen and glucose to the heart and the large skeletal muscles. The result is physiological support for adaptive behaviors such as "fight or flight." Immune responses to stressful situations may be part of these adaptive responses because, in addition to the risk inherent in the situation (e.g., a predator), fighting and fleeing carries the risk of injury and subsequent entry of infectious agents into the bloodstream or skin. Any wound in the skin is likely to contain pathogens that could multiply and cause infection (Williams & Leaper, 1998). Stress-induced changes in the immune system that could accelerate wound repair and help prevent infections from taking hold would therefore be adaptive and selected along with other physiological changes that increased evolutionary fitness.Modern humans rarely encounter many of the stimuli that commonly evoked fight-or-flight responses for their ancestors, such as predation or inclement weather without protection. However, human physiological response continues to reflect the demands of earlier environments. Threats that do not require a physical response (e.g., academic exams) may therefore have physical consequences, including changes in the immune system. Indeed, over the past 30 years, more than 300 studies have been done on stress and immunity in humans, and together they have shown that psychological challenges are capable of modifying various features of the immune response. In this article we attempt to consolidate empirical knowledge about psychological stress and the human immune system through meta-analysis. Both the construct of stress and the human immune system are complex, and both could consume bookCorrespondence concerning this article should be addressed to Suzanne C. Segerstrom, Department of Ps...

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Age-related changes in immune parameters in a very old population of Swedish people: A longitudinal study

Cited by 124 publications

References 7 publications

Aging Down-Regulates the Transcription Factor E2A, Activation-Induced Cytidine Deaminase, and Ig Class Switch in Human B Cells

Aging Down-Regulates the Transcription Factor E2A, Activation-Induced Cytidine Deaminase, and Ig Class Switch in Human B Cells

B cells and immunosenescence: A focus on IgG+IgD−CD27− (DN) B cells in aged humans

Psychological Stress and the Human Immune System: A Meta-Analytic Study of 30 Years of Inquiry.

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