Cancerous inhibitor of Protein Phosphatase 2A promotes B-cell activation in vitro. Mus musculus

The generation of optimal immune response requires combined activation of both T- and B-cells. Here, we demonstrate that the cancerous inhibitor of protein phosphatase 2A (CIP2A) is a novel factor that governs activation of both T- and B-cells in vivo. Upon ovalbumin challenge, CIP2A-deficient (CIP2AHOZ) mice show impaired immune response. Furthermore, CIP2AHOZ mice had impaired clearance of Listeria Monocytogenesis (L.m.) infection, combined with decreased numbers of CD8+ T-cells and IFN-γ secretion. In an ovalbumin model of allergic asthma, CIP2AHOZ B-cells were impaired in IgE and IgG secretion, despite of normal Th2 differentiation and unaffected numbers of inflammatory cells or cytokines in bronchoalveolar lavage. Importantly, the cell-autonomous effect of CIP2A deficiency for both T- and B-cell activation was confirmed by in vitro assays. During the T-cell activation CIP2A, was shown to promote expression of ETS-1, whereas in B-cells CIP2A loss resulted in inhibition of MYC-mediated gene expression. Together these results identify CIP2A as a novel cell-autonomous regulator governing both T- and B-cell activation in vivo. They also identify CIP2AHOZ as a novel murine model for investigation of impaired immune response and allergic asthma. Overall design: This dataset consists of samples used in two separate studies. Samples were normalized together, but only total RNA obtained from 2 mutant mice was compared to 2 wild type controls (CIP2A-LacZ; TK13) was used for determination of CIP2A role in B- & T- cell immunity. Whilst, only total RNA obtained from 2 mutant lymphoma bearing mice was compared to 2 wild type lymphom bearing controls (CIP2A-LacZ*Emu-myc; TKEM) for determination of CIP2A role in B-cell lymphoma .