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

R Nahar, P Ramezani-Rad, M Mossner… - Blood, The Journal …, 2011 - ashpublications.org
R Nahar, P Ramezani-Rad, M Mossner, C Duy, L Cerchietti, H Geng, S Dovat, H Jumaa
Blood, The Journal of the American Society of Hematology, 2011ashpublications.org
Initial cell surface expression of the pre-B cell receptor induces proliferation. After 2 to 5
divisions, however, large pre-BII (Fraction C') cells exit cell cycle to become resting, small
pre-BII cells (Fraction D). 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 chain gene recombination and to prevent malignant transformation into acute
lymphoblastic leukemia. Here we demonstrate that inducible activation of pre-B cell receptor …
Abstract
Initial cell surface expression of the pre-B cell receptor induces proliferation. After 2 to 5 divisions, however, large pre-BII (Fraction C') cells exit cell cycle to become resting, small pre-BII cells (Fraction D). 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 chain gene recombination and to prevent malignant transformation into acute lymphoblastic leukemia. Here we demonstrate that inducible activation of pre-B cell receptor signaling induces cell-cycle exit through up-regulation of the transcriptional repressor BCL6. Inducible activation of BCL6 downstream of the pre-B cell receptor results in transcriptional repression of MYC and CCND2. Hence, pre-B cell receptor-mediated activation of BCL6 limits pre-B cell proliferation and induces cellular quiescence at the small pre-BII (Fraction D) stage.
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