Essential role of phospholipase Cγ2 in early B-cell development and Myc-mediated lymphomagenesis

Renren Wen, Yuhong Chen, Li Bai, Guoping Fu, James Schuman, Xuezhi Dai, Hu Zeng, Chunying Yang, Robert P. Stephan, John L. Cleveland, Demin Wang

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

Phospholipase Cγ2 (PLCγ2) is a critical signaling effector of the B-cell receptor (BCR). Here we show that PLCγ2 deficiency impedes early B-cell development, resulting in an increase of B220+ CD43 + BP-1+ CD24hi pre-BCR+ large pre-B cells. PLCγ2 deficiency impairs pre-BCR-mediated functions, leading to enhanced interleukin-7 (IL-7) signaling and elevated levels of RAGs in the selected large pre-B cells. Consequently, PLCγ2 deficiency renders large pre-B cells susceptible to transformation, resulting in dramatic acceleration of Myc-induced lymphomagenesis. PLCγ2-/- Eμ-Myc transgenic mice mainly develop lymphomas of B220+ CD43+ BP-1 + CD24hi pre-B-cell large pre-B-cell origin, which are uncommon in wild-type Eμ-Myc transgenics. Furthermore, lymphomas from PLCγ2-/- Eμ-Myc transgenic mice exhibited a loss of p27 Kip1 and often displayed alterations in Arf or p53. Thus, PLCγ2 plays an important role in pre-BCR-mediated early B-cell development, and its deficiency leads to markedly increased pools of the most at-risk large pre-B cells, which display hyperresponsiveness to IL-7 and express high levels of RAGs, making them prone to secondary mutations and Myc-induced malignancy.

Original languageEnglish (US)
Pages (from-to)9364-9376
Number of pages13
JournalMolecular and cellular biology
Volume26
Issue number24
DOIs
StatePublished - Dec 1 2006

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ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Wen, R., Chen, Y., Bai, L., Fu, G., Schuman, J., Dai, X., Zeng, H., Yang, C., Stephan, R. P., Cleveland, J. L., & Wang, D. (2006). Essential role of phospholipase Cγ2 in early B-cell development and Myc-mediated lymphomagenesis. Molecular and cellular biology, 26(24), 9364-9376. https://doi.org/10.1128/MCB.00839-06