Work

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

Year: 2003

Type: article

Abstract: 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 kappa rearrangement. These alterations were accompanied by tyrosine phosphorylation of immunoglobulin beta 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.

Source: The Journal of Experimental Medicine

DOI: 10.1084/jem.20030729

Authors: Theresa Tretter, Ashley E. Ross, Dominic I. Dordai, Stephen Desiderio

Institutions: Howard Hughes Medical Institute, Johns Hopkins University

Language: English

Topic: T-cell and B-cell Immunology

Subfield: Immunology

Field: Immunology and Microbiology

Domain: Life Sciences

Open Access status: green

Funder: National Cancer Institute

Awards: G1890337441, Program on Molecular and Cellular Mechanisms of Tumorigenesis