Regulation of B lymphocyte development and activation by Bruton's tyrosine kinase

Research output: Contribution to journalArticle

92 Scopus citations

Abstract

The generation and maintenance of B lymphocytes is controlled by biochemical signals transmitted by the B cell antigen receptor (BCR) complex. These signals are transduced by multiple cytoplasmic protein tyrosine kinases (PTKs) including Lyn, Syk, and Bruton's tyrosine kinase (BTK). Upon BCR engagement, these PTKs activate downstream effectors, including transcription factors that modulate gene expression. In turn, activation of downstream effectors is critical for B cell survival, cell cycle progression, and antibody production. Our studies focus on the role of BTK in these biological responses. We have discovered that BTK is required for activation of the BCR-responsive transcription factor, NF-κB. Furthermore, BTK-dependent activation of NF-κB is essential for reprogramming the expression of genes that control B cell survival and proliferation. The biochemical mechanisms by which BTK regulates signaling components that activate NF-κB, and the identification of BTK-responsive genes are under investigation. Elucidation of these regulatory mechanisms is expected to reveal new therapeutic targets for B cell pathologies involving defects in BTK, including X-linked agammaglobulinemia (XLA).

Original languageEnglish (US)
Pages (from-to)147-156
Number of pages10
JournalImmunologic Research
Volume23
Issue number2-3
DOIs
StatePublished - Jul 5 2001
Externally publishedYes

    Fingerprint

Keywords

  • B Cell Receptor
  • B Lymphocyte
  • Bruton's Tyrosine Kinase
  • Transcription Factors
  • X-Linked Agammaglobulinemia(XLA)
  • X-Linked Immunodeficiency (Xid)

ASJC Scopus subject areas

  • Immunology

Cite this