Pim2 attenuates IL-7-driven proliferation in cells with RAG DSBs. (A) RAG1^−/−:IgH:Bcl2, Artemis^−/−:IgH:Bcl2, and Artemis^−/−:Pim2^−/−:IgH:Bcl2 were cultured in IL-7 and the percent of cells in S phase was assessed by BrdU incorporation. Shown is the mean and standard deviation for two replicates. (B–C) Artemis^−/−:Pim2^−/−:IgH:Bcl2 (B) and RAG1^−/−:IgH:Bcl2 (C) pre–B cells were transduced with an empty retroviral vector (empty) or retrovirus expressing Pim2 (Pim2). Cells were cultured in IL-7 and the percent of S-phase cells was assessed by BrdU incorporation 3 d after retroviral transduction. Shown is the mean and standard deviation of two replicates. Data in A, B, and C are representative of at least three experiments. (D) Model illustrating context-dependent roles of Pim1 and Pim2 in developing pre–B cells. Red lines represent inhibition and black arrows designate activation. Pim1 and Akt activity are triggered by IL-7 receptor signals. These two kinases cooperate to support pre–B cell survival through phosphorylation of BAD and subsequent inactivation of BAX. Expression of Pim1 also supports IL-7–driven proliferation. Loss of IL-7 leads to loss of Pim1 and Akt activities, expression of RAG, and initiation of IgLκ chain gene rearrangement. RAG DSBs activate ATM, which induces Pim2 expression. Pim2 phosphorylates BAD and blocks pre–B cell proliferation.