BTK Signaling in B Cell Differentiation and Autoimmunity.
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.
Department of Pulmonary Medicine, Erasmus MC Rotterdam, Room Ee2251a, PO Box 2040, NL 3000, CA, Rotterdam, The Netherlands.
Odilia B J
OBJ
Corneth
Department of Pulmonary Medicine, Erasmus MC Rotterdam, Room Ee2251a, PO Box 2040, NL 3000, CA, Rotterdam, The Netherlands.
Roel G J
RGJ
Klein Wolterink
Department of Pulmonary Medicine, Erasmus MC Rotterdam, Room Ee2251a, PO Box 2040, NL 3000, CA, Rotterdam, The Netherlands. r.hendriks@erasmusmc.nl.
Rudi W
RW
Hendriks
D000077329:Agammaglobulinaemia Tyrosine Kinase; D000361:Agammaglobulinemia / Q000201:enzymology* / Q000235:genetics / Q000276:immunology / Q000503:physiopathology; D000818:Animals; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000166:cytology / Q000201:enzymology* / Q000276:immunology; D002454:Cell Differentiation; D040181:Genetic Diseases, X-Linked / Q000201:enzymology* / Q000235:genetics / Q000276:immunology / Q000503:physiopathology; D006801:Humans; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction
D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human