BTK Signaling in B Cell Differentiation and Autoimmunity

Curr Top Microbiol Immunol. 2016;393:67-105. doi: 10.1007/82_2015_478.


Since the original identification of Bruton's tyrosine kinase (BTK) as the gene defective in the primary immunodeficiency X-linked agammaglobulinemia (XLA) in 1993, our knowledge on the physiological function of BTK has expanded impressively. In this review, we focus on the role of BTK during B cell differentiation in vivo, both in the regulation of expansion and in the developmental progression of pre-B cells in the bone marrow and as a crucial signal transducer of signals downstream of the IgM or IgG B cell antigen receptor (BCR) in mature B cells governing proliferation, survival, and differentiation. In particular, we highlight BTK function in B cells in the context of host defense and autoimmunity. Small-molecule inhibitors of BTK have very recently shown impressive anti-tumor activity in clinical studies in patients with various B cell malignancies. Since promising effects of BTK inhibition were also seen in experimental animal models for lupus and rheumatoid arthritis, BTK may be a good target for controlling autoreactive B cells in patients with systemic autoimmune disease.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Agammaglobulinaemia Tyrosine Kinase
  • Agammaglobulinemia / enzymology*
  • Agammaglobulinemia / genetics
  • Agammaglobulinemia / immunology
  • Agammaglobulinemia / physiopathology
  • Animals
  • Autoimmunity*
  • B-Lymphocytes / cytology
  • B-Lymphocytes / enzymology*
  • B-Lymphocytes / immunology
  • Cell Differentiation*
  • Genetic Diseases, X-Linked / enzymology*
  • Genetic Diseases, X-Linked / genetics
  • Genetic Diseases, X-Linked / immunology
  • Genetic Diseases, X-Linked / physiopathology
  • Humans
  • Protein-Tyrosine Kinases / genetics
  • Protein-Tyrosine Kinases / immunology*
  • Signal Transduction


  • Protein-Tyrosine Kinases
  • Agammaglobulinaemia Tyrosine Kinase
  • BTK protein, human

Supplementary concepts

  • Bruton type agammaglobulinemia