Apoptosis and its modulation during B lymphopoiesis in mouse bone marrow

Lü, Lei; Osmond, Dennis G.

doi:10.1111/j.1600-065x.2000.imr017506.x

Cited by 106 publications

(133 citation statements)

References 91 publications

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“…For multiple-color flow cytometric analysis, cell samples were stained with antibodies specific for phenotypic markers as previously described [47] with the following anti-mouse mAb (BD PharMingen, San Diego, CA): anti-Annexin V-FITC, antiCD11c-FITC (clone HL3), anti-CD4-PE (clone GK1.5), anti-I-A/ I-E-PE (anti-MHC-II-PE, clone M5/114.15.2), anti-CD40-PE (clone 3/23), anti-CD80-PE (anti-B7-1-PE, clone 16-10A1), anti-CD86-PE (anti-B7-2-PE, clone 16-10A1), anti-I-A/I-E-PECy5 (anti-MHC-II-PE-Cy5, clone M5/114.15.2), anti-TLR4 (CD284/MD2 complex, clone MTS 510) and isotype-matched antibodies as negative controls. Biotinylated anti-Ob-R (clone 9F8), its isotype-matched control antibody and streptavidin-FITC were purchased from R&D systems.…”

Section: Immunostainingmentioning

confidence: 99%

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Involvement of leptin signaling in the survival and maturation of bone marrow‐derived dendritic cells

et al. 2006

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Previous studies demonstrated that lymphocyte development is impaired in leptin receptor (Ob-R)-deficient db/db mice. However, it remains unclear whether or not leptin signaling plays a physiological role in dendritic cell (DC) development and function. In this study, we first detected Ob-R expression in murine DC. Using db/db mice at a pre-diabetic stage, we demonstrate that the total number of DC generated from bone marrow (BM) cultures is significantly lower than in WT controls. Similarly, selective blockade of leptin with a soluble mouse Ob-R chimera (Ob-R:Fc) inhibited DC generation in wild-type BM cultures. The reduced DC yield in db/db BM culture was attributed to significantly increased apoptosis, which was associated with dysregulated expression of Bcl-2 family genes. Moreover, db/db DC displayed markedly reduced expression of co-stimulatory molecules and a Th2-type cytokine profile, with a poor capacity to stimulate allogeneic T cell proliferation. Consistent with their impaired DC phenotype and function, db/db DC showed significantly down-regulated activities of the PI3K/Akt pathway as well as STAT-3 and IjB-a. In conclusion, our findings demonstrate the involvement of leptin signaling in DC survival and maturation.See accompanying commentary: http://dx

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Section: Immunostainingmentioning

confidence: 99%

“…In separate experiments, cell samples were fixed and incubated in 50 lg/mL RNase (Roche Diagnostics GmbH, Mannheim, Germany) and 50 lg/mL propidium iodide (Sigma Aldrich) before flow cytometric analysis. Hypodiploid cells were identified as apoptotic cells by gating on the sub-G 1 peak in the DNA histogram, as described [47].…”

Section: Apoptosis Assaymentioning

confidence: 99%

Involvement of leptin signaling in the survival and maturation of bone marrow‐derived dendritic cells

et al. 2006

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“…If lymphocyte growth and proliferation are allowed to proceed in excess, oncogenesis [1] or autoimmunity can occur [2]. In contrast, if too much apoptosis occurs, degenerative or immunodeficiency disease may arise [3][4][5]. To regulate this balance, tissue-specific growth factors are required to provide cell survival and growth signals [6].…”

Section: Introductionmentioning

confidence: 99%

Activated Akt promotes increased resting T cell size, CD28‐independent T cell growth, and development of autoimmunity and lymphoma

et al. 2003

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The mechanisms that regulate basal T cell size and metabolic activity are uncertain. Since the phosphatidylinositol-3 phosphate kinase (PI3 K) and Akt (PKB) pathway has been shown in model organisms to regulate both cell size and metabolism, we generated transgenic mice expressing a constitutively active form of Akt (myristoylated Akt, mAkt) in T cells. Naive transgenic T cells were enlarged and had increased rates of glycolysis compared to control T cells. In addition, mAkt transgenic T cells resisted death-by-neglect upon in vitro culture. Upon activation, mAkt-transgenic T cells were less dependent than control cells on costimulation through CD28 and could both grow rapidly and secrete cytokines in the absence of CD28 ligation. In addition, transgenic expression of mAkt led to the accumulation of CD4 T cells and B cells with age. Many aged mAkt-transgenic mice also developed autoimmunity with immunoglobulin deposits on kidney glomeruli and displayed increased incidence of lymphoma. Together, these data show that Akt activation is sufficient to increase basal T cell size and metabolism. Enhancement of T cell metabolism by Akt and more rapid CD28-independent T cell growth may contribute to the accumulation of excess immune cells and the development of lymphoma and autoimmunity.

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“…[1][2][3][4]. Lymphoid progenitors, including the earliest detectable B cell progenitors, are found in a fraction of bone marrow cells which express the ␣ subunit of the IL-7R (IL-7R␣), low levels of c-Kit, and variable levels of terminal deoxynucleotidyl transferase (4,5).…”

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confidence: 99%

Analysis of Gene Expression and Ig Transcription in PU.1/Spi-B-Deficient Progenitor B Cell Lines

Schweitzer

DeKoter

2004

The Journal of Immunology

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A number of presumptive target genes for the Ets-family transcription factor PU.1 have been identified in the B cell lineage. However, the precise function of PU.1 in B cells has not been studied because targeted null mutation of the PU.1 gene results in a block to lymphomyeloid development at an early developmental stage. In this study, we take advantage of recently developed PU.1−/−Spi-B−/− IL-7 and stromal cell-dependent progenitor B (pro-B) cell lines to analyze the function of PU.1 and Spi-B in B cell development. We show that contrary to previously published expectations, PU.1 and/or Spi-B are not required for Ig H chain (IgH) gene transcription in pro-B cells. In fact, PU.1−/−Spi-B−/− pro-B cells have increased levels of IgH transcription compared with wild-type pro-B cells. In addition, high levels of Igκ transcription are induced after IL-7 withdrawal of wild-type or PU.1−/−Spi-B−/− pro-B cells. In contrast, we found that Igλ transcription is reduced in PU.1−/−Spi-B−/− pro-B cells relative to wild-type pro-B cells after IL-7 withdrawal. These results suggest that Igλ, but not IgH or Igκ, transcription, is dependent on PU.1 and/or Spi-B. The PU.1−/−Spi-B−/− pro-B cells have other phenotypic changes relative to wild-type pro-B cells including increased proliferation, increased CD25 expression, decreased c-Kit expression, and decreased RAG-1 expression. Taken together, our observations suggest that reduction of PU.1 and/or Spi-B activity in pro-B cells promotes their differentiation to a stage intermediate between late pro-B cells and large pre-B cells.

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Apoptosis and its modulation during B lymphopoiesis in mouse bone marrow

Cited by 106 publications

References 91 publications

Involvement of leptin signaling in the survival and maturation of bone marrow‐derived dendritic cells

Involvement of leptin signaling in the survival and maturation of bone marrow‐derived dendritic cells

Activated Akt promotes increased resting T cell size, CD28‐independent T cell growth, and development of autoimmunity and lymphoma

Analysis of Gene Expression and Ig Transcription in PU.1/Spi-B-Deficient Progenitor B Cell Lines

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