Age effects on B cells and humoral immunity in humans

Abstract

Both humoral and cellular immune responses are impaired in aged individuals, leading to decreased vaccine responses. Although T cell defects occur, defects in B cells play a significant role in age-related humoral immune changes. The ability to undergo class switch recombination (CSR), the enzyme for CSR, AID (activation-induced cytidine deaminase) and the transcription factor E47 are all decreased in aged stimulated B cells. We here present an overview of agerelated changes in human B cell markers and functions, and also discuss some controversies in the field of B cell aging.

Effects of aging on human leukocytes (part II): immunophenotyping of adaptive immune B and T cell subsets

“…Furthermore, a decrease in classswitched B cells and decrease in affinity antibodies has been observed in the elderly (Frasca et al 2008). The decrease in humoral protection links B cells, similar to T cells, with immunosenescence (Bulati et al 2011;Frasca et al 2011).…”

“…Although the total numbers of mature B cells decrease with age (reviewed in Frasca et al 2011), conflicting reports on the ratio of naïve and memory cells exists (Kolar et al 2006;Caraux et al 2010;Bulati et al 2011;Frasca et al 2011). Furthermore, a decrease in classswitched B cells and decrease in affinity antibodies has been observed in the elderly (Frasca et al 2008).…”

Reversing T cell immunosenescence: why, who, and how

“…In older adults with CMV seropositivity, up to 25% of the total CD8+ T cells pool is specific for CMV immunodominant epitopes (Pawelec et al 2009;Virgin et al 2009). This expansion of CMV-specific CD8 + is associated with the loss of the costimulatory molecule CD28 which has been reported as key predictor of immune incompetence in older individuals (Vallejo 2005;Frasca et al 2011). CD28 marker is expressed constitutively on >99% of human T cells at birth.…”

“…The CD154 ligand has been shown to induce cytokine production, costimulate proliferation of activated T cells and this accompanied by production of IFN-γ, TNF-α, and IL-2. Hence the capacity of these cells to help in B cell proliferation and antibody production is considerably reduced contributing to the impairment of humoral response in the aged (Haynes 2005;Lang et al 2010b;Frasca et al 2011). Globally, the proliferative capacity of CD28 − T cells is also limited; these cells have shortened telomeres and show increased resistance to apoptosis and restricted T cell diversity and are named senescent cells (Vallejo 2005).…”

“…Although individuals' age is a major contributor, there is no single cause of immunosenescence, which is the consequence of a compilation of events (Govind et al 2012) including thymic involution , the continuous reshaping of the immune repertoire by persistent antigenic challenges (Virgin et al 2009), the dysregulation of Toll-like receptor functions (Shaw et al 2011), the reduced production of naïve B cells and the intrinsic defects arising in resident B cells (Frasca et al 2011), and the impact of nutritional status and dysregulation of hormonal pathways (Kelley et al 2007;Lang and Samaras 2012). Moreover, human aging is also inextricably linked with an ever increasing incidence of chronic-comorbid health conditions (e.g., diabetes and heart failure) which contribute to increase the age-related chronic low-grade inflammation and therefore further impinge the immune system (Fulop et al 2010;Franceschi et al 2007).…”