Immunity
Volume 17, Issue 4, October 2002, Pages 473-485
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Article
Control of Pre-BCR Signaling by Pax5-Dependent Activation of the BLNK Gene

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Abstract

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 Igμ transgenic Pax5−/− pro-B cells resulted in constitutive pre-BCR signaling and increased cell proliferation without inducing progression to the pre-B cell stage. Igμ+ 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.

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Present address: AgResearch, Crown Research Institute, Private Bag 3123, Hamilton, New Zealand.