Control of pre-BCR signaling by Pax5-dependent activation of the BLNK gene

被引:132
作者
Schebesta, M [1 ]
Pfeffer, PL [1 ]
Busslinger, M [1 ]
机构
[1] Vienna Bioctr, Res Inst Mol Pathol, A-1030 Vienna, Austria
关键词
D O I
10.1016/S1074-7613(02)00418-1
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The developmental progression from pro-B to pre-B cells is controlled by pre-B cell receptor (pre-BCR) signaling which depends on BLNK (SLP-65) for coupling the Syk kinase to its downstream effector pathways. Here we identified BLNK as a direct target of the transcription factor Pax5 (BSAP). Restoration of BLNK expression in Igmu transgenic Pax5(-/-) pro-B cells resulted in constitutive pre-BCR signaling and increased cell proliferation without inducing progression to the pre-B cell stage. Igmu(+) Pax5(-/-) pro-B cells expressing a BLNK-estrogen receptor fusion protein initiated signaling immediately upon hormone addition, which facilitated analysis of pre-BCR-induced gene expression changes. The pre-BCR was shown to execute its checkpoint function by regulating genes involved in cell proliferation, intracellular signaling, growth factor responsiveness, and V(D)J recombination.
引用
收藏
页码:473 / 485
页数:13
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