The inositol phosphatase SHIP negatively regulates late stage B-cell development and class switch recombination

SHIP is a haemopoietic‐specific phosphatase that regulates antigen receptor, growth factor and cytokine‐mediated cell activation. Mice with germline deletion of SHIP develop a lethal pathology caused by myeloid cell dysregulation. To determine SHIP's role in B cells while avoiding the pheitropic phenotype of SHIP‐null mice, we have bred SHIP‐floxed mice to CD19cre mice. CD19cre SHIP‐floxed mice have less mature B cells in the bone marrow due to a faster rate of maturation of SHIP‐deficient B cells. We also observe that B cells that lack SHIP have activated phenotypes and generate switched antibodies, particularly IgG2a, in the periphery even in the absence of high affinity antigen. In contrast, mice with B cell specific deletion of SHIP exhibit hyporesponsiveness to both T‐cell dependent and T‐independent immunizations. Overall these results suggest that SHIP‐deficient B cells have lower thresholds of spontaneous activation and cytokine stimulation while at the same time they become more refractory to foreign antigen stimulation.