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In order to generate an immune response against myeloma cells in an homogenous murine model, a stable hybrid cell line (DCSp) was established through the syngenic fusion between mouse dendritic cells (DC) and mouse Sp2/0 myeloma cells. DCSp cells behaved as potent T cell stimulators and were able to induce Sp2/0 specific cytotoxicity. When mice were immunized with irradiated hybrids before SP2/0 injection, they exhibited a significantly higher rate of survival as compared with controls. When tumors were detected, their emergence was not delayed, and time elapsed between tumor clinical perception and death remained unchanged. A humoral immune response was also always associated. We assume that this stable dendritoma cell line can be considered a valuable tool for myeloma studies in an homogenous mouse model. The efficiency of dendritoma as a weapon against tumor cells and the benefit of syngeny in experimental models are discussed. [ABSTRACT FROM AUTHOR]

Inositol 1,4,5-trisphosphate 3-kinase B (or Itpkb) and inositol 1,3,4,5-tetrakisphosphate (Ins(1,3,4,5)P4), its reaction product, play an important role in the control of B lymphocyte fate and function in vivo. In order to investigate the fine mechanisms of Itpkb and Ins(1,3,4,5)P4 action in B cells, we crossed Itpkb(-/-) mice with transgenic mice expressing a 3-83μδ B cell receptor (BCR) specific for membrane-bound MHC-I H2-K(b) and H2-K(k) molecules. On a non-deleting H2-K(d) genetic background, we show that Itpkb is important for the control of Bim protein expression and B cell survival rather than for the control of B cell development from one stage to another. Analyses of cell surface markers expression, proapoptotic Bim protein expression, in vitro survival and in vivo turnover demonstrated that BCR transgenic Itpkb(-/-) B cells exhibit an anergic phenotype with the notable exception of their enhanced antigen-induced calcium signalling. On a deleting H2-K(b) genetic background, we show that Itpkb is not essential for BCR editing or negative selection. These data establish Itpkb as an important regulator of B cell survival and anergy in vivo., (Copyright © 2010 Elsevier GmbH. All rights reserved.)

Background: Eosinophils are key players in T(H)2-driven pathologies, such as allergic lung inflammation. After IL-5- and eotaxin-mediated tissue recruitment, they release several cytotoxic and inflammatory mediators. However, their exact contribution to asthma remains controversial. Indeed, in human subjects anti-IL-5 treatment inhibits eosinophilia but not antigen-induced airway hyperresponsiveness (AHR). Likewise, lung fibrosis is abrogated in 2 strains of eosinophil-deficient mice, whereas AHR is inhibited in only one of them. Finally, eosinophils have been shown to attract T(H)2 lymphocytes at the inflammatory site., Objective: The ability of eosinophils to promote AHR and lung inflammation independently of lymphocytes was investigated., Methods: Adoptive transfers of resting or activated eosinophils from IL-5 transgenic mice were performed into naive BALB/c mice, mice with severe combined immunodeficiency, and IFN-gamma-deficient BALB/c recipients., Results: Adoptively transferred eosinophils induced lung inflammation, fibrosis, collagen deposition, and AHR not only in BALB/c mice but also in recipient mice with severe combined immunodeficiency. Surprisingly, IFN-gamma expression was increased in lungs from eosinophil-transferred animals. Furthermore, IFN-gamma neutralization in recipients partially inhibited eosinophil-induced AHR. Moreover, IFN-gamma-deficient eosinophils or eosinophils treated with a blocking anti-IFN-gamma receptor antibody failed to induce AHR in IFN-gamma-deficient recipients. Finally, in vitro and at low concentrations, IFN-gamma increased eosinophil peroxidase release, potentiated chemotaxis, and prolonged survival, suggesting the existence of an autocrine mechanism., Conclusions: These results support the important and previously unsuspected contribution of eosinophils to lung inflammation independently of lymphocytes through production of IFN-gamma, the prototypical T(H)1 cytokine.

There is evidence that the shape of cells and their contact with a matrix direct the growth and the differentiation of both normal and cancer cells. Cells in 3D culture resemble the in vivo situation more closely than do those in conventional 2D cultures. We have studied the interactions and functions of B16F10 mouse melanoma cells, which spread and grow well on tissue culture polystyrene (tPS), when they were made to aggregate on cellulose-coated Petri dishes (CEL). This aggregation of melanoma cells on CEL was Ca2+ dependent and mediated by N-cadherins. The levels of N-cadherin and beta-catenin transcripts in cells cultured on CEL and tPS were similar, but those on CEL contained less beta-catenin protein. Immunoprecipitation and immunostaining showed that both N-cadherins and beta-catenins were present at the membranes of cells on CEL. Cells proliferated significantly more slowly after 48 h on CEL and the cellulose coating caused most of them to arrest in G1. We also compared the melanin contents and tyrosinase activity of cells on CEL and controls grown on tPS. Melanogenesis was induced in cells aggregated on CEL. A cellulose substrate thus appears to be an outstanding tool for studying cell-cell interactions and cell functions in 3D cultures.

In order to generate an immune response against myeloma cells in an homogenous murine model, a stable hybrid cell line (DCSp) was established through the syngenic fusion between mouse dendritic cells (DC) and mouse Sp2/0 myeloma cells. DCSp cells behaved as potent T cell stimulators and were able to induce Sp2/0 specific cytotoxicity. When mice were immunized with irradiated hybrids before SP2/0 injection, they exhibited a significantly higher rate of survival as compared with controls. When tumors were detected, their emergence was not delayed, and time elapsed between tumor clinical perception and death remained unchanged. A humoral immune response was also always associated. We assume that this stable dendritoma cell line can be considered a valuable tool for myeloma studies in an homogenous mouse model. The efficiency of dendritoma as a weapon against tumor cells and the benefit of syngeny in experimental models are discussed.