An important role of phospholipase Cγ1 in pre-B-cell development and allelic exclusion

被引:33
作者
Wen, RR
Chen, YH
Schuman, J
Fu, GP
Yang, S
Zhang, WG
Newman, DK
Wang, DM
机构
[1] Blood Ctr SE Wisconsin Inc, Blood Res Inst, Milwaukee, WI 53226 USA
[2] Nanjing Univ, Inst Mol Med, Model Res Anim Ctr, Nanjing 210008, Peoples R China
[3] Duke Univ, Med Ctr, Dept Immunol, Durham, NC USA
[4] Med Coll Wisconsin, Dept Microbiol & Mol Genet, Milwaukee, WI 53226 USA
关键词
allelic exclusion; B-cell development; phospholipase C gamma 1; pre-B-cell receptor;
D O I
10.1038/sj.emboj.7600405
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Phospholipase Cgamma1 (PLCgamma1) has been reported to be expressed predominantly in T cells and to play an important role in T-cell receptor signaling. Here we show that PLCgamma1 is expressed throughout B-cell development, with high expression in B-cell progenitors, and is involved in pre-B- cell receptor (pre-BCR) signaling. Reduced expression of PLCgamma1, in the absence of PLCgamma2 (PLCgamma1(+/-)PLCgamma2(-/-)), impedes early B-cell development at the pro-B- to pre-B-cell transition and impairs immunoglobulin heavy chain allelic exclusion, hallmarks of defective pre-BCR signaling. In contrast, early B-cell development is largely normal, whereas late B-cell maturation is impaired in the absence of PLCgamma2 alone (PLCgamma2(-/-)) and overexpression of PLCgamma1 in PLCgamma2(-/-) mice fails to restore BCR-mediated B-cell proliferation and maturation. These studies reveal an essential role of PLCgamma1, distinct from that of PLCgamma2, in B-cell development.
引用
收藏
页码:4007 / 4017
页数:11
相关论文
共 49 条
[1]  
Bae SS, 1998, J NEUROCHEM, V71, P178
[2]   PREDOMINANT EXPRESSION AND ACTIVATION-INDUCED TYROSINE PHOSPHORYLATION OF PHOSPHOLIPASE C-GAMMA-2 IN LYMPHOCYTES-B [J].
COGGESHALL, KM ;
MCHUGH, JC ;
ALTMAN, A .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (12) :5660-5664
[3]   Impaired immunoglobulin gene rearrangement in mice lacking the IL-7 receptor [J].
Corcoran, AE ;
Riddell, A ;
Krooshoop, D ;
Venkitaraman, AR .
NATURE, 1998, 391 (6670) :904-907
[4]   The adaptor protein SLP-65 acts as a tumor suppressor that limits pre-B cell expansion [J].
Flemming, A ;
Brummer, T ;
Reth, M ;
Jumaa, H .
NATURE IMMUNOLOGY, 2003, 4 (01) :38-43
[5]   BLNK: a central linker protein in B cell activation [J].
Fu, C ;
Turck, CW ;
Kurosaki, T ;
Chan, AC .
IMMUNITY, 1998, 9 (01) :93-103
[6]   ALTERED IMMUNOGLOBULIN EXPRESSION AND FUNCTIONAL SILENCING OF SELF-REACTIVE LYMPHOCYTES-B IN TRANSGENIC MICE [J].
GOODNOW, CC ;
CROSBIE, J ;
ADELSTEIN, S ;
LAVOIE, TB ;
SMITHGILL, SJ ;
BRINK, RA ;
PRITCHARDBRISCOE, H ;
WOTHERSPOON, JS ;
LOBLAY, RH ;
RAPHAEL, K ;
TRENT, RJ ;
BASTEN, A .
NATURE, 1988, 334 (6184) :676-682
[7]   B cell development pathways [J].
Hardy, RR ;
Hayakawa, K .
ANNUAL REVIEW OF IMMUNOLOGY, 2001, 19 :595-621
[8]   Cutting edge:: Essential role of phospholipase C-γ2 in B cell development and function [J].
Hashimoto, A ;
Takeda, K ;
Inaba, M ;
Sekimata, M ;
Kaisho, T ;
Ikehara, S ;
Homma, Y ;
Akira, S ;
Kurosaki, T .
JOURNAL OF IMMUNOLOGY, 2000, 165 (04) :1738-1742
[9]   Positive versus negative signaling by lymphocyte antigen receptors [J].
Healy, JI ;
Goodnow, CC .
ANNUAL REVIEW OF IMMUNOLOGY, 1998, 16 :645-670
[10]  
HEMPEL WM, 1992, J IMMUNOL, V148, P3021