The ageing human B cell repertoire: a failure of selection?

Dunn‐Walters, Deborah K.

doi:10.1111/cei.12700

Cited by 63 publications

(62 citation statements)

References 57 publications

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“…Once committed to the B lineage, B cell precursors must undergo immunoglobulin gene rearrangement during the pre- and pro-B cell stages, followed by expression of the B cell receptor (BCR) to become an immature B cell and exiting the bone marrow [36]. In the periphery, immature B cells undergo further selective pressure during transitional stages before completing maturation.…”

Section: B Cell Selection Mechanisms With Agementioning

confidence: 99%

Lymphocyte generation and population homeostasis throughout life

Yanes

Gustafson

Weyand

et al. 2017

Seminars in Hematology

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Immune aging is a multi-faceted process that manifests as reduced competence to fight infections and malignant cells as well as diminished tissue repair, unprovoked inflammation and increased autoreactivity. The aging adaptive immune system, with its high complexity in functional cell subpopulations and diversity of B and T cell receptors, has to cope with the challenge of maintaining homeostasis while responding to exogenous stimuli and compensating for reduced generative capacity. With thymic involution, naïve T cells begin to function as quasi-stem cells and maintain the compartment through peripheral homeostatic proliferation that shapes the T cell repertoire through peripheral selection and the activation of differentiation pathways. Similarly, reduced generation of early B cell progenitors alters the composition of the peripheral B cell compartment with the emergence of a unique, auto-inflammatory B cell subset, termed age-associated B cells (ABCs). These changes in T and B cell composition and function are core manifestations of immune aging.

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Section: B Cell Selection Mechanisms With Agementioning

confidence: 99%

Lymphocyte generation and population homeostasis throughout life

Yanes

Gustafson

Weyand

et al. 2017

Seminars in Hematology

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“…Despite reduced tonsil GC B cells (Lee et al, ), most elderly people can maintain the capacity to generate a diverse B‐cell repertoire (Kolar, Mehta, Wilson, & Capra, ). Similarly to TCR, the BCR repertoire in humans has been shown to decline with age and becomes dysfunctional (de Bourcy et al, ; Boyd, Liu, Wang, Martin, & Dunn‐Walters, ; Dunn‐Walters, ; Wang et al, ). A shift in T‐cell and B‐cell subtypes from naïve to memory, a significant increase in circulating regulatory CD4 T cells (Tregs) (Freitas et al, ), and changes in T‐cell and B‐cell signaling have been described in elderly individuals (Beatriz Suarez‐Alvarez, ; Le Page, Dupuis, Larbi, Mitwowski, & Fulop, ; Naylor et al, ).…”

Section: Introductionmentioning

confidence: 99%

Compromised steady‐state germinal center activity with age in nonhuman primates

et al. 2019

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Age-related reductions in vaccine-induced B cells in aging indicate that germinalcenters (GCs), the anatomical site where the development of humoral responses takes place, may lose efficacy with age. We have investigated the baseline follicular and GC composition in nonhuman primates (NHPs) with respect to their age. There was a marked reduction in follicular area in old animals. We found significantly lower normalized numbers of follicular PD1 hi CD4 T (Tfh) and proliferating (Ki67 hi ) GC B cells with aging, a profile associated with significantly higher numbers of potential follicular suppressor FoxP3 hi Lag3 hi CD4 T cells. Furthermore, a positive correlation was found between Tfh and follicular CD8 T cells (fCD8) only in young animals.Despite the increased levels of circulating preinflammatory factors in aging, young animals had higher numbers of monocytes and granulocytes in the follicles, a profile negatively associated with numbers of Tfh cells. Multiple regression analysis showed an altered association between GC B cells and other GC immune cell populations in old animals suggesting a differential mechanistic regulation of GC activity in aging.Our data demonstrate defective baseline GC composition in old NHPs and provide an immunological base for further understanding the adaptive humoral responses with respect to aging.

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“…Studies of B-cell receptors (BCR) in peripheral blood have shown that the B-cell repertoire of aging subjects is characterized by reduced BCR diversity, which is correlated with poor health status. Moreover, BCR repertoire diversity seems to be reduced in lymph nodes from aging subjects, whereas in spleen samples, the diversity was rather larger in aging than in young individuals [17,18] .…”

Section: Cd25mentioning

confidence: 93%

Zika Virus Infection in the Elderly: Possible Relationship with Guillain-Barré Syndrome

Savino

Messias²,

Mendes-da-Cruz³

et al. 2016

Gerontology

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The Zika virus (ZIKV) outbreak in French Polynesia, in 2013, and in Brazil, in 2015, was correlated with neurological complications, which comprised, among others, congenital microcephaly and Guillain-Barré syndrome (GBS), which includes a group of acute autoimmune neuropathies generally reported after respiratory or gastrointestinal infectious diseases. Despite being relatively rare, the incidence rate of GBS rises with age, which makes GBS more frequent in the elderly, in whom it is also a more severe disease with slower recovery than in younger patients. Different forms of GBS have been described having diagnostic confirmation of a previous infection with the ZIKV virus. Although we do not have enough evidence that elderly people are a particularly susceptible population to developing GBS following ZIKV infection, this is plausible. We should consider this possibility, particularly taking into account that aging subjects are more susceptible to infections. In this context, a deeper understanding of how the immune system in the elderly functions in relation to ZIKV infection is necessary, as well as an understanding of what kind of alterations of the nervous system such an infection triggers in the elderly, beyond GBS. This will be relevant for better therapeutic interventions and for designing vaccine candidates that can be applied in an aging population, particularly those prone to develop ZIKV-induced autoimmunity.

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The ageing human B cell repertoire: a failure of selection?

Cited by 63 publications

References 57 publications

Lymphocyte generation and population homeostasis throughout life

Lymphocyte generation and population homeostasis throughout life

Compromised steady‐state germinal center activity with age in nonhuman primates

Zika Virus Infection in the Elderly: Possible Relationship with Guillain-Barré Syndrome

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