Mimicry of Pre–B Cell Receptor Signaling by Activation of the Tyrosine Kinase Blk

Autor: Tretter, Theresa, Ross, Ashley E., Dordai, Dominic I., Desiderio, Stephen
Zdroj: The Journal of Experimental Medicine; December 2003, Vol. 198 Issue: 12 p1863-1873, 11p
Abstrakt: During B lymphoid ontogeny, assembly of the pre–B cell receptor (BCR) is a principal developmental checkpoint at which several Src-related kinases may play redundant roles. Here the Src-related kinase Blk is shown to effect functions associated with the pre-BCR. B lymphoid expression of an active Blk mutant caused proliferation of B progenitor cells and enhanced responsiveness of these cells to interleukin 7. In mice lacking a functional pre-BCR, active Blk supported maturation beyond the pro–B cell stage, suppressed VH to DJH rearrangement, relieved selection for productive heavy chain rearrangement, and stimulated κ rearrangement. These alterations were accompanied by tyrosine phosphorylation of immunoglobulin β and Syk, as well as changes in gene expression consistent with developmental maturation. Thus, sustained activation of Blk induces responses normally associated with the pre-BCR.
Databáze: Supplemental Index