Pre-B cell receptor–mediated activation of BCL6 induces pre-B cell quiescence through transcriptional repression of MYC

Initial cell surface expression of the pre- B cell receptorinduces proliferation. After 2 to 5 divisions, however, large pre-BII (Fraction C') cells exit cell cycleto become resting, small pre-BII cells( FractionD). The mechanism by which pre-BII cells exit cell cycle, however, is currently unclear. The checkpoint at the Fraction C'-D transition is critical for immunoglobulin light chaingene recombination and to prevent malignant transformationinto acute lymphoblastic leukemia. Here we demonstrate that inducible activation of pre- B cell receptorsignaling induces cell-cycleexit through up-regulation of the transcriptional repressor BCL6. Inducible activation of BCL6downstream of the pre- B cell receptorresults in transcriptional repression of MYC and CCND2 . Hence, pre- B cell receptor-mediated activation of BCL6limits pre- B cellproliferation and induces cellular quiescence at the small pre-BII (Fraction D) stage.