Pax5 maintains cellular identity by repressing gene expression throughout B cell differentiation

被引:17
作者
Carotta, Sebastian
Holmes, Melissa L.
Pridans, Clare
Nutt, Stephen L.
机构
[1] Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Parkville, Vic 3050, Australia
[2] Univ Western Sydney, Richmond, NSW, Australia
关键词
Pax5; repression; lineage commitment; Flt3; pro-B cell; Blimp-1; c-fms;
D O I
10.4161/cc.5.21.3396
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The transcription factor Pax5 is required for many aspects of B-lymphopoiesis including lineage commitment, immunoglobulin rearrangement, pre-BCR signalling and mature B cell survival. Pax5 regulates B cell lineage commitment by concurrently activating B cell specific gene expression as well as suppressing the expression of genes associated with non-B cell fates. The identity of the molecular targets of Pax5-mediated gene repression is the subject of much current interest. Recent studies have documented the essential nature of the Pax5 mediated repression of the stem cell transcriptional program, as well as the silencing of lineage inappropriate gene expression, for B cell development. Surprisingly the repression of genes by Pax5 continues throughout lymphopoiesis, with the loss of Pax5 in mature B cell resulting in the reactivation of the same Pax5 targets during plasma cell differentiation. These recent insights into the mechanism of action of Pax5 in controlling B cell identity will be discussed.
引用
收藏
页码:2452 / 2456
页数:5
相关论文
共 49 条
[1]   PAX-5 ENCODES THE TRANSCRIPTION FACTOR BSAP AND IS EXPRESSED IN LYMPHOCYTES-B, THE DEVELOPING CNS, AND ADULT TESTIS [J].
ADAMS, B ;
DORFLER, P ;
AGUZZI, A ;
KOZMIK, Z ;
URBANEK, P ;
MAURERFOGY, I ;
BUSSLINGER, M .
GENES & DEVELOPMENT, 1992, 6 (09) :1589-1607
[2]   Upregulation of flt3 expression within the bone marrow Lin-Sca1+c-kit+ stem cell compartment is accompanied by loss of self-renewal capacity [J].
Adolfsson, J ;
Borge, OJ ;
Bryder, D ;
Theilgaard-Mönch, K ;
Åstrand-Grundström, I ;
Sitnicka, E ;
Sasaki, Y ;
Jacobsen, SEW .
IMMUNITY, 2001, 15 (04) :659-669
[3]   Identification of Flt3+ lympho-myeloid stem cells lacking erythro-megakaryocytic potential:: A revised road map for adult blood lineage commitment [J].
Adolfsson, J ;
Månsson, R ;
Buza-Vidas, N ;
Hultquist, A ;
Liuba, K ;
Jensen, CT ;
Bryder, D ;
Yang, LP ;
Borge, OJ ;
Thoren, LAM ;
Anderson, K ;
Sitnicka, E ;
Sasaki, Y ;
Sigvardsson, M ;
Jacobsen, SEW .
CELL, 2005, 121 (02) :295-306
[4]   Frontline:: A B220+ CD117+ CD19- hematopoietic progenitor with potent lymphoid and myeloid developmental potential [J].
Balciunaite, G ;
Ceredig, R ;
Massa, S ;
Rolink, AG .
EUROPEAN JOURNAL OF IMMUNOLOGY, 2005, 35 (07) :2019-2030
[5]   Transcriptional control of early B cell development [J].
Busslinger, M .
ANNUAL REVIEW OF IMMUNOLOGY, 2004, 22 :55-79
[6]  
CALAME KL, 2003, ANNU REV IMMUNOL, V8, P8
[7]   Increasing Flt3L availability alters composition of a novel bone marrow lymphoid progenitor compartment [J].
Ceredig, Rhodri ;
Rauch, Melanie ;
Balciunaite, Gina ;
Rolink, Antonius G. .
BLOOD, 2006, 108 (04) :1216-1222
[8]   Pax5 determines B- versus T-cell fate and does not block early myeloid-lineage development [J].
Cotta, CV ;
Zhang, Z ;
Kim, HG ;
Klug, CA .
BLOOD, 2003, 101 (11) :4342-4346
[9]   PU.1 regulates expression of the interleukin-7 receptor in lymphoid progenitors [J].
DeKoter, RP ;
Lee, HJ ;
Singh, H .
IMMUNITY, 2002, 16 (02) :297-309
[10]   Gene repression by Pax5 in B cells is essential for blood cell homeostasis and is reversed in plasma cells [J].
Delogu, A ;
Schebesta, A ;
Sun, Q ;
Aschenbrenner, K ;
Perlot, T ;
Busslinger, M .
IMMUNITY, 2006, 24 (03) :269-281