Aged mice exhibit distinct B cell precursor phenotypes differing in activation, proliferation and apoptosis

Put, Elaine Van der; Sherwood, Erin M.; Blomberg, Bonnie B.; Riley, Richard L.

doi:10.1016/j.exger.2003.07.003

Cited by 40 publications

(78 citation statements)

References 22 publications

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“…Furthermore, some losses in pro-B cell fractions have also been observed (1,3,4,6,8,19). Pro-B/ early pre-B cells express the CD43 surface Ag together with the B lineage Ags CD45R (B220) and CD19 as well as CD95 (AA4.1) and are negative for surface IgM (19).…”

Section: Aged B Cell Precursors Exhibit Reduced E47 Protein In Vivo Amentioning

confidence: 97%

“…Protein extraction reagent was supplemented with Halt Protease Inhibitor Cocktail (Pierce) at 10 l/ml. For phospho-ERK (P-ERK) 3 analysis, total cell lysates also contained 2 mM Na 3 VO 4 . Extracts of IL-7-expanded pro-B/ pre-B cells were denatured by boiling for 4 min in sample buffer, subjected to reducing conditions, and electrophoresed using SDS-PAGE 4 -12% polyacrylamide gels for 50 min at 200 V. Proteins were run out on gels, then transferred onto nitrocellulose membranes for 90 min at 100 V. Nonspecific sites were blocked by incubation of the membranes with PBSTween 20 (1ϫ PBS/0.05% Tween 20) containing 10% milk for 2 h at room temperature.…”

Section: Immunoprecipitation and Western Blot Analysismentioning

confidence: 99%

“…BALB/c mice by ϳ2 years of age generally show a variable loss in late-stage pre-B cells (1)(2)(3)(4)(5)(6)(7)(8). Furthermore, some losses in pro-B cell fractions have also been observed (1,3,4,6,8,19).…”

Section: Aged B Cell Precursors Exhibit Reduced E47 Protein In Vivo Amentioning

confidence: 99%

“…A s mice age, the process of B lymphopoiesis diminishes substantially (1)(2)(3)(4)(5)(6)(7)(8). By 2 years of age, marked losses are apparent in the late pre-B cell compartment and, in a subset of aged mice, within the pro-B cell compartments as well (3,4,6,8).…”

mentioning

confidence: 99%

“…By 2 years of age, marked losses are apparent in the late pre-B cell compartment and, in a subset of aged mice, within the pro-B cell compartments as well (3,4,6,8). The decline in B lymphopoiesis in senescent mice coincides with reduced expression of RAG-2 and capacity to rearrange genes at the V H loci (5-7).…”

mentioning

confidence: 99%

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Accelerated Notch-Dependent Degradation of E47 Proteins in Aged B Cell Precursors Is Associated with Increased ERK MAPK Activation

King

Put

Blomberg

et al. 2007

The Journal of Immunology

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The transcriptional regulator E47, encoded by the E2A gene, is crucial to B lymphopoiesis. In BALB/c senescent mice (∼2 years old), the incidence of E47-expressing pro-B cells in vivo and E47 protein steady state levels in B cell precursors in vitro were reduced. Poor expression of E47 protein was a consequence of accelerated proteasome-mediated turnover and was associated with heightened ubiquitin modification of E2A-encoded proteins in aged B cell precursors. Both MAPK and Notch activity have been previously associated with E2A-encoded protein stability in lymphocytes. Aged B cell precursors exhibited heightened levels of MAPK activity reflected in increased levels of phospho-ERK proteins. Phosphorylation of E2A-encoded proteins was also increased in aged B cell precursors and pharmacologic inhibition of MEK-1 resulted in a partial restoration of their E47 protein. Both Notch proteins and their Delta-like ligands were detected comparably in young and aged B cell precursors. Either inhibition of Notch activation via gamma-secretase or Ab blockade of Notch-Delta-like ligand interactions partially restored E47 expression in aged B cell precursors. We hypothesize that increased MAPK activity promotes phosphorylation of E2A-encoded protein in aged B cell precursors. Subsequently, E2A-encoded proteins undergo ubiquitination and accelerated degradation in a Notch-dependent process. The dysregulation of E2A-encoded protein expression may contribute to the reductions seen in early B lymphopoiesis during murine senescence.

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Section: Aged B Cell Precursors Exhibit Reduced E47 Protein In Vivo Amentioning

confidence: 97%

Section: Immunoprecipitation and Western Blot Analysismentioning

confidence: 99%

Section: Aged B Cell Precursors Exhibit Reduced E47 Protein In Vivo Amentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Accelerated Notch-Dependent Degradation of E47 Proteins in Aged B Cell Precursors Is Associated with Increased ERK MAPK Activation

King

Put

Blomberg

et al. 2007

The Journal of Immunology

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Aged mice exhibit distinct peripheral B‐cell phenotypes differing in apoptotic susceptibility: An ex vivo analysis

Verdier¹,

Malissein²,

E³

et al. 2006

Cytometry Pt A

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Background: Age-related changes in the antibody response have been classically associated with alterations in T-cell help, but increasing evidence shows that intrinsic B-cell defects exist. This article analyzes the apoptotic susceptibility of peripheral B-cells in aged and young control mice. Materials and Methods: Freshly isolated lymphocytes from spleen and Peyer's patches (PPs) were labeled for Bcell lineage (B220 1 cells) and germinal center B subset (GCs, B2201 /PNA 1 cells). Alternatively, splenic B-cells purified by MACS were used. Apoptosis was monitored by the Annexin V binding, incorporation of 3,3 0 -dihexyloxacarbocyanine iodide (DiOC 6 (3)), propidium iodide (PI) staining, and morphological changes. Moreover, intracellular Bcl-2 expression and Bad phosphorylation status were also analyzed in B-cells. Results: We showed in aging mice an enhanced Annexin V

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The effects of proliferation and DNA damage on hematopoietic stem cell function determine aging

Khurana

2016

Developmental Dynamics

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In most of the mammalian tissues, homeostasis as well as injury repair depend upon a small number of resident adult stem cells. The decline in tissue/organ function in aged organisms has been directly linked with poorly functioning stem cells. Altered function of hematopoietic stem cells (HSCs) is at the center of an aging hematopoietic system, a tissue with high cellular turnover. Poorly engrafting, myeloid-biased HSCs with higher levels of DNA damage accumulation are the hallmark features of an aged hematopoietic system. These cells show a higher proliferation rate than their younger counterparts. It was proposed that quiescence of these cells over long period of time leads to accumulation of DNA damage, eventually resulting in poor function/pathological conditions in hematopoietic system. However, various mouse models with premature aging phenotype also show highly proliferative HSCs. This review examines the evidence that links proliferation of HSCs with aging, which leads to functional changes in the hematopoietic system. Developmental Dynamics 245:739-750,

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Aged mice exhibit distinct B cell precursor phenotypes differing in activation, proliferation and apoptosis

Cited by 40 publications

References 22 publications

Accelerated Notch-Dependent Degradation of E47 Proteins in Aged B Cell Precursors Is Associated with Increased ERK MAPK Activation

Accelerated Notch-Dependent Degradation of E47 Proteins in Aged B Cell Precursors Is Associated with Increased ERK MAPK Activation

Aged mice exhibit distinct peripheral B‐cell phenotypes differing in apoptotic susceptibility: An ex vivo analysis

The effects of proliferation and DNA damage on hematopoietic stem cell function determine aging

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