Medical College of Wisconsin
CTSICores SearchResearch InformaticsREDCap

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

10/13/2006

Pubmed ID

17030619

Pubmed Central ID

PMC1698523

DOI

10.1128/MCB.00839-06

Scopus ID

2-s2.0-33845383712   23 Citations

Abstract

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 D

Authors

Demin Wang PhD Assistant Professor in the Microbiology and Immunology department at Medical College of Wisconsin
Renren Wen PhD Associate Investigator in the Blood Research Institute department at BloodCenter of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
B-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
jenkins-FCD Prod-400 0f9a74600e4e79798f8fa6f545ea115f3dd948b2