B cell precursors are decreased in senescent   mice, but retain normal mitotic activity in vivo and in vitro

Riley, Richard L.; Kruger, Mark G.; Elia, Jeanne

doi:10.1016/0090-1229(91)90026-7

Cited by 83 publications

(75 citation statements)

References 12 publications

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“…It is well established that senescence in mice results in impaired B lymphopoiesis (1)(2)(3)(4)(5)(6)(7)(8). This is primarily seen as a loss of pre-B cells, but also affects both the development of immature B cells and the readout of the B cell specificity repertoire (3, 28 -30).…”

Section: Discussionmentioning

confidence: 99%

“…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%

“…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%

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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: Discussionmentioning

confidence: 99%

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

confidence: 97%

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

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

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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“…Age related changes in bone marrow B cell commitment and development include declines in the frequency of precursors, lowered expression of key genes, reductions in pro-and pre-B cell compartments, and attenuated responsiveness to differentiation factors (Frasca, Nguyen et al 2004;Labrie, Sah et al 2004;Miller, Izon et al 2002;Riley, Kruger et al 1991;Sherwood, Xu et al 2000;Stephan, Reilly et al 1998;Stephan, Sanders et al 1996;Szabo, Shen et al 2003). Overall, these findings suggest reductions in the generation and throughput of B cell progenitors.…”

Section: B Lineage Progenitors Decline With Age Suggesting New Homeomentioning

confidence: 99%

B cells and aging: Balancing the homeostatic equation

Miller

Cancro

2007

Experimental Gerontology

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The interplay of selective and homeostatic processes dominates the behavior of B lineage subsets following B cell antigen receptor (BCR) expression, and extends to determinants of immune response quality and the persistence of immunologic memory. A key concept emerging from these considerations is that primary events acting upstream of mature B lymphocyte pools can profoundly impact downstream populations as the system attempts homeostatic adjustments. Since advancing age is accompanied by profound changes in B cell generation and homeostasis, establishing the relative contributions of primary lesions versus compensatory homeostatic processes is critical to understanding these perturbations. Exploration of this problem requires an understanding of: 1) the identity, dynamics, and progenitor/successor relationships of marrow and peripheral B cell subsets; 2) the nature and interactions of selective and homeostatic processes acting in these subsets; and 3) how these change with age. Our data show that BLyS and its receptors mediate peripheral B cell homeostasis, and that the size, dynamics and behavior of all B cell subsets influenced by B Lymphocyte Stimulator change with age. These findings suggest that homeostatic processes mediated through B Lymphocyte Stimulator are altered with age, and that these perturbations may primarily reflect compensatory homeostatic adjustments to upstream reductions in B cell generation.

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Alveolar bone turnover in male rats: Site‐ and age‐specific changes

et al. 1995

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We conclude that the bone turnover dynamics adjacent to maxillary first molars represent predominantly remodeling on the distal in both groups and modeling on the mesial only in the young rats, that distal molar tooth drift reflects alveolar bone turnover, and that alveolar bone manifests the marked reduction in bone cell activity that occurs in the rat skeleton after 8 weeks but that this reduction is compensated by recruitment or maintenance of more bone cells at these sites.

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B cell precursors are decreased in senescent mice, but retain normal mitotic activity in vivo and in vitro

Cited by 83 publications

References 12 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

B cells and aging: Balancing the homeostatic equation

Alveolar bone turnover in male rats: Site‐ and age‐specific changes

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