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Spleen-dependent turnover of CD11b peripheral blood B lymphocytes in bovine leukemia virus-infected sheep.

ABSTRACT: Lymphocyte homeostasis is determined by a critical balance between cell proliferation and death, an equilibrium which is deregulated in bovine leukemia virus (BLV)-infected sheep. We have previously shown that an excess of proliferation occurs in lymphoid tissues and that the peripheral blood population is prone to increased cell death. To further understand the mechanisms involved, we evaluated the physiological role of the spleen in this accelerated turnover. To this end, B lymphocytes were labeled in vivo using a fluorescent marker (carboxyfluorescein diacetate succinimidyl ester), and the cell kinetic parameters (proliferation and death rates) of animals before and after splenectomy were compared. We show that the enhanced cell death observed in BLV-infected sheep is abrogated after splenectomy, revealing a key role of the spleen in B-lymphocyte dynamics.

SUBMITTER: Florins A

PROVIDER: S-EPMC1676270 | biostudies-literature | 2006 Dec

REPOSITORIES: biostudies-literature

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Spleen-dependent turnover of CD11b peripheral blood B lymphocytes in bovine leukemia virus-infected sheep.

Florins Arnaud A Gillet Nicolas N Asquith Becca B Debacq Christophe C Jean Geneviève G Schwartz-Cornil Isabelle I Bonneau Michel M Burny Arsène A Reichert Michal M Kettmann Richard R Willems Luc L

Journal of virology 20061011 24

Lymphocyte homeostasis is determined by a critical balance between cell proliferation and death, an equilibrium which is deregulated in bovine leukemia virus (BLV)-infected sheep. We have previously shown that an excess of proliferation occurs in lymphoid tissues and that the peripheral blood population is prone to increased cell death. To further understand the mechanisms involved, we evaluated the physiological role of the spleen in this accelerated turnover. To this end, B lymphocytes were la ...[more]

PMID: 17035334

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Project description:Presented are the results of a study of the expression pattern of different proteins in the course of bovine leukemia virus-induced leukemia in experimental sheep and I discuss how the obtained data may be useful in gaining a better understanding of the pathogenesis of the disease, diagnosis, and for the selection of possible therapeutic targets. In cattle, the disease is characterized by life-long persistent lymphocytosis leading to leukemia/lymphoma in about 5% of infected animals. In sheep, as opposed to cattle, the course of the disease is always fatal and clinical symptoms usually occur within a three-year period after infection. For this reason, sheep are an excellent experimental model of retrovirus-induced leukemia. This model can be useful for human pathology, as bovine leukemia virus is closely related to human T-lymphotropic virus type 1. The data presented here provide novel insights into the molecular mechanisms of the bovine leukemia virus-induced tumorigenic process and indicate the potential marker proteins both for monitoring progression of the disease and as possible targets of pharmacological intervention. A study of the proteome of B lymphocytes from four leukemic sheep revealed 11 proteins with altered expression. Among them, cytoskeleton and intermediate filament proteins were the most abundant, although proteins belonging to the other functional groups, i.e. enzymes, regulatory proteins, and transcription factors, were also present. It was found that trypsin inhibitor, platelet factor 4, thrombospondin 1, vasodilator-stimulated phosphoprotein, fibrinogen alpha chain, zyxin, filamin-A, and vitamin D-binding protein were downregulated, whereas cleavage and polyadenylation specificity factor subunit 5, non-POU domain-containing octamer-binding protein and small glutamine-rich tetratricopeptide repeat-containing protein alpha were upregulated. Discussed are the possible mechanisms of their altered expression and its significance in the bovine leukemia virus-induced leukemogenic process. Impact statement The submitted manuscript provides new data on the molecular mechanisms of BLV-induced tumorigenic process indicating the potential marker proteins both for monitoring the progression of the disease and as possible targets of pharmacological intervention. This is to my knowledge the first study of the proteome of the transformed lymphocytes in the course of bovine leukemia virus-induced leukemia in susceptible animals. BLV can be considered as useful model for related human pathogen - HTLV-1, another member of the deltaretrovirus genus evolutionary closely related to BLV. Information gathered in this study can be useful to speculate on possible shared mechanisms of deltaretrovirus-induced carcinogenesis.

Dataset Information

Spleen-dependent turnover of CD11b peripheral blood B lymphocytes in bovine leukemia virus-infected sheep.

Publications

Spleen-dependent turnover of CD11b peripheral blood B lymphocytes in bovine leukemia virus-infected sheep.

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