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

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. 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 .