Essential role of phospholipase C gamma 2 in early B-cell development and Myc-mediated lymphomagenesis. Mol Cell Biol 2006 Dec;26(24):9364-76
Date
10/13/2006Pubmed ID
17030619Pubmed Central ID
PMC1698523DOI
10.1128/MCB.00839-06Scopus ID
2-s2.0-33845383712 (requires institutional sign-in at Scopus site) 30 CitationsAbstract
Phospholipase Cgamma2 (PLCgamma2) is a critical signaling effector of the B-cell receptor (BCR). Here we show that PLCgamma2 deficiency impedes early B-cell development, resulting in an increase of B220+ CD43+ BP-1+ CD24hi pre-BCR+ large pre-B cells. PLCgamma2 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, PLCgamma2 deficiency renders large pre-B cells susceptible to transformation, resulting in dramatic acceleration of Myc-induced lymphomagenesis. PLCgamma2(-/-) Emu-Myc transgenic mice mainly develop lymphomas of B220+ CD43+ BP-1+ CD24hi pre-BCR+ large pre-B-cell origin, which are uncommon in wild-type Emu-Myc transgenics. Furthermore, lymphomas from PLCgamma2(-/-) Emu-Myc transgenic mice exhibited a loss of p27Kip1 and often displayed alterations in Arf or p53. Thus, PLCgamma2 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.
Author List
Wen R, Chen Y, Bai L, Fu G, Schuman J, Dai X, Zeng H, Yang C, Stephan RP, Cleveland JL, Wang DMESH terms used to index this publication - Major topics in bold
AnimalsB-Lymphocytes
Cell Differentiation
Isoenzymes
Lymphoma
Membrane Glycoproteins
Mice
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Phospholipase C gamma
Pre-B Cell Receptors
Proto-Oncogene Proteins c-myc
Receptors, Antigen, B-Cell
