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

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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

51 Scopus citations

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 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.

Original languageEnglish (US)
Pages (from-to)1863-1873
Number of pages11
JournalJournal of Experimental Medicine
Volume198
Issue number12
DOIs
StatePublished - Dec 15 2003

Keywords

  • Allelic exclusion
  • B cell development
  • Signal transduction
  • Src kinases
  • V(D)J recombination

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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