Scripps VIVO scripps research logo

  • Index
  • Log in
  • Home
  • People
  • Organizations
  • Research
  • Events
Search form

Essential role of phospholipase c gamma 2 in early b-cell development and myc-mediated lymphomagenesis

Academic Article
uri icon
  • Overview
  • Identity
  • Additional Document Info
  • View All
scroll to property group menus

Overview

authors

  • Wen, R. R.
  • Chen, Y. H.
  • Bai, L.
  • Fu, G. P.
  • Schuman, J.
  • Dai, X. Z.
  • Zeng, H.
  • Yang, C. Y.
  • Stephan, R. P.
  • Cleveland, John
  • Wang, D. M.

publication date

  • December 2006

journal

  • Molecular and Cellular Biology  Journal

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.

subject areas

  • 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
scroll to property group menus

Identity

International Standard Serial Number (ISSN)

  • 0270-7306

Digital Object Identifier (DOI)

  • 10.1128/mcb.00839-06

PubMed ID

  • 17030619
scroll to property group menus

Additional Document Info

start page

  • 9364

end page

  • 9376

volume

  • 26

issue

  • 24

©2021 The Scripps Research Institute | Terms of Use | Powered by VIVO

  • About
  • Contact Us
  • Support