BTK Signaling in B Cell Differentiation and Autoimmunity

Current Topics in Microbiology and Immunology
Odilia B J CornethR W Hendriks

Abstract

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.

Citations

Aug 27, 2019·Frontiers in Immunology·Kata P SzilveszterAttila Mócsai
Dec 26, 2016·International Archives of Allergy and Immunology·Gholamreza AziziAsghar Aghamohammadi
Sep 22, 2018·Frontiers in Immunology·Sara Roman-GarciaYolanda R Carrasco
Jul 12, 2019·Frontiers in Immunology·Dario DidonaMichael Hertl
Feb 2, 2021·Frontiers in Immunology·Maria A Bacalao, Anne B Satterthwaite
May 1, 2020·Journal of Medicinal Chemistry·Emily J HananSteven T Staben
May 1, 2021·Journal of Clinical Medicine·Salem AlmaaniDavid Jayne
Aug 27, 2021·Frontiers in Medicine·Thomas Schmitt, Jens Waschke
Sep 10, 2021·Neurology. Neuroimmunology and Neuroinflammation·Martin S WeberMichael R Yeaman

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