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

Rahul Nahar, Parham Ramezani-Rad, Maximilian Mossner, Cihangir Duy, Leandro Cerchietti, Huimin Geng, Sinisa Dovat, Hassan Jumaa, B. Hilda Ye, Ari Melnick, Markus Müschen

Research output: Contribution to journalArticle

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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 upregulation 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.

Original languageEnglish (US)
Pages (from-to)4174-4178
Number of pages5
JournalBlood
Volume118
Issue number15
DOIs
StatePublished - Oct 13 2011

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Pre-B Cell Receptors
B-Lymphoid Precursor Cells
Chemical activation
Cells
Cell Cycle
Immunoglobulin Light Chain Genes
Cell signaling
Immunoglobulin Light Chains
Cell proliferation
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Genetic Recombination
Up-Regulation
Genes
Cell Proliferation

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Nahar, R., Ramezani-Rad, P., Mossner, M., Duy, C., Cerchietti, L., Geng, H., ... Müschen, M. (2011). Pre-B cell receptor-mediated activation of BCL6 induces pre-B cell quiescence through transcriptional repression of MYC. Blood, 118(15), 4174-4178. https://doi.org/10.1182/blood-2011-01-331181

Pre-B cell receptor-mediated activation of BCL6 induces pre-B cell quiescence through transcriptional repression of MYC. / Nahar, Rahul; Ramezani-Rad, Parham; Mossner, Maximilian; Duy, Cihangir; Cerchietti, Leandro; Geng, Huimin; Dovat, Sinisa; Jumaa, Hassan; Ye, B. Hilda; Melnick, Ari; Müschen, Markus.

In: Blood, Vol. 118, No. 15, 13.10.2011, p. 4174-4178.

Research output: Contribution to journalArticle

Nahar, R, Ramezani-Rad, P, Mossner, M, Duy, C, Cerchietti, L, Geng, H, Dovat, S, Jumaa, H, Ye, BH, Melnick, A & Müschen, M 2011, 'Pre-B cell receptor-mediated activation of BCL6 induces pre-B cell quiescence through transcriptional repression of MYC', Blood, vol. 118, no. 15, pp. 4174-4178. https://doi.org/10.1182/blood-2011-01-331181
Nahar, Rahul ; Ramezani-Rad, Parham ; Mossner, Maximilian ; Duy, Cihangir ; Cerchietti, Leandro ; Geng, Huimin ; Dovat, Sinisa ; Jumaa, Hassan ; Ye, B. Hilda ; Melnick, Ari ; Müschen, Markus. / Pre-B cell receptor-mediated activation of BCL6 induces pre-B cell quiescence through transcriptional repression of MYC. In: Blood. 2011 ; Vol. 118, No. 15. pp. 4174-4178.
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