Cutting edge:: The PI3K p110δ is required for down-regulation of RAG expression in immature B cells

被引:43
作者
Llorian, Miriam [1 ]
Stamataki, Zania [1 ]
Hill, Susan [1 ]
Turner, Martin [1 ]
Martensson, Inga-Lill [1 ]
机构
[1] Babraham Inst, Lab Lymphocyte Signalling & Dev, Cambridge CB2 4AT, England
基金
英国生物技术与生命科学研究理事会; 英国医学研究理事会;
关键词
D O I
10.4049/jimmunol.178.4.1981
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
At the immature B cell stage the BCR signals the down-regulation of the RAG genes and Ig L chain (LC) allelic and isotype exclusion. The signaling pathway that regulates these events is poorly characterized. We demonstrate that immature B cells from mice deficient in the PI3K catalytic subunit p110 delta fail to suppress RAG expression and inappropriately recombine K and A LC loci. In addition, in the presence of the autoantigen, clonal deletion and receptor editing still takes place, demonstrating that these processes are independent of p110 delta. These results demonstrate a role for p110 delta in the regulation of RAG gene expression and thereby LC alleliclisotype exclusion. The journal of Immunology, 2007,178:1981-1985.
引用
收藏
页码:1981 / 1985
页数:5
相关论文
共 29 条
[1]   Resolution of three nonproliferative immature splenic B cell subsets reveals multiple selection points during peripheral B cell maturation [J].
Allman, D ;
Lindsley, RC ;
DeMuth, W ;
Rudd, K ;
Shinton, SA ;
Hardy, RR .
JOURNAL OF IMMUNOLOGY, 2001, 167 (12) :6834-6840
[2]   A crucial role for the p110δ subunit of phosphatidylinositol 3-kinase in B cell development and activation [J].
Clayton, E ;
Bardi, G ;
Bell, SE ;
Chantry, D ;
Downes, CP ;
Gray, A ;
Humphries, LA ;
Rawlings, D ;
Reynolds, H ;
Vigorito, E ;
Turner, M .
JOURNAL OF EXPERIMENTAL MEDICINE, 2002, 196 (06) :753-763
[3]   Phosphoinositide 3-kinase and its targets in B-cell and T-cell signaling [J].
Fruman, DA .
CURRENT OPINION IN IMMUNOLOGY, 2004, 16 (03) :314-320
[4]   DOWN-REGULATION OF RAG1 AND RAG2 GENE-EXPRESSION IN PREB CELLS AFTER FUNCTIONAL IMMUNOGLOBULIN HEAVY-CHAIN REARRANGEMENT [J].
GRAWUNDER, U ;
LEU, TMJ ;
SCHATZ, DG ;
WERNER, A ;
ROLINK, AG ;
MELCHERS, F ;
WINKLER, TH .
IMMUNITY, 1995, 3 (05) :601-608
[5]   A conserved transcriptional enhancer regulates RAG gene expression in developing B cells [J].
Hsu, LY ;
Lauring, J ;
Liang, HE ;
Greenbaum, S ;
Cado, D ;
Zhuang, Y ;
Schlissel, MS .
IMMUNITY, 2003, 19 (01) :105-117
[6]   REGULATION OF V(D)J RECOMBINATION ACTIVATOR PROTEIN RAG-2 BY PHOSPHORYLATION [J].
LIN, WC ;
DESIDERIO, S .
SCIENCE, 1993, 260 (5110) :953-959
[7]   The tyrosine kinase Syk is required for light chain isotype exclusion but dispensable for the negative selection of B cells [J].
Meade, J ;
Tybulewicz, VLJ ;
Turner, M .
EUROPEAN JOURNAL OF IMMUNOLOGY, 2004, 34 (04) :1102-1110
[8]  
Meade J, 2002, EUR J IMMUNOL, V32, P1029, DOI 10.1002/1521-4141(200204)32:4<1029::AID-IMMU1029>3.0.CO
[9]  
2-M
[10]   Antibody regulation of B cell development [J].
Meffre, E ;
Casellas, R ;
Nussenzweig, MC .
NATURE IMMUNOLOGY, 2000, 1 (05) :379-385