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

23 Citations (Scopus)

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
Externally publishedYes

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Phospholipases
B-Lymphoid Precursor Cells
B-Lymphocytes
Pre-B Cell Receptors
Interleukin-7
Transgenic Mice
Lymphoma
B-Lymphocyte Subsets
Mutation
Neoplasms

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Essential role of phospholipase Cγ2 in early B-cell development and Myc-mediated lymphomagenesis. / Wen, Renren; Chen, Yuhong; Bai, Li; Fu, Guoping; Schuman, James; Dai, Xuezhi; Zeng, Hu; Yang, Chunying; Stephan, Robert P.; Cleveland, John L.; Wang, Demin.

In: Molecular and Cellular Biology, Vol. 26, No. 24, 01.12.2006, p. 9364-9376.

Research output: Contribution to journalArticle

Wen, R, Chen, Y, Bai, L, Fu, G, Schuman, J, Dai, X, Zeng, H, Yang, C, Stephan, RP, Cleveland, JL & Wang, D 2006, 'Essential role of phospholipase Cγ2 in early B-cell development and Myc-mediated lymphomagenesis', Molecular and Cellular Biology, vol. 26, no. 24, pp. 9364-9376. https://doi.org/10.1128/MCB.00839-06
Wen, Renren ; Chen, Yuhong ; Bai, Li ; Fu, Guoping ; Schuman, James ; Dai, Xuezhi ; Zeng, Hu ; Yang, Chunying ; Stephan, Robert P. ; Cleveland, John L. ; Wang, Demin. / Essential role of phospholipase Cγ2 in early B-cell development and Myc-mediated lymphomagenesis. In: Molecular and Cellular Biology. 2006 ; Vol. 26, No. 24. pp. 9364-9376.
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