BTK Signaling in B Cell Differentiation and Autoimmunity

  • Odilia B. J. Corneth
  • Roel G. J. Klein Wolterink
  • Rudi W. HendriksEmail author
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 393)


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.



Antibody-producing cell


B cell activating factor


B cell adapter for PI3K


B cell receptor


Bone marrow-expressed kinase


Bruton’s tyrosine kinase


Collagen-induced arthritis


Chronic lymphocytic leukemia




Endoplasmic reticulum


Extracellular signal-regulated kinase


Germinal center


Germline transcripts


Growth factor receptor-bound 2

H chain

Heavy chain






Inositol 1,4,5-trisphosphate


Immunoreceptor tyrosine-based activation motif


Inducible T cell kinase

L chain

Light chain




Lck/Yes novel tyrosine kinase


Mitogen-activated protein kinase


Mantle cell lymphoma


Nuclear factor of activated T cells


Phosphoinositide 3-kinase


Phosphatidylinositol 4,5-bisphosphate


Phosphatidylinositol 3,4,5,-triphosphate


Protein kinase C β


Phospholipase C γ


Phosphatase and tensin homologue


Rheumatoid arthritis


Resting lymphocyte kinase

SH2 domain

Src homology 2 domain

SH3 domain

Src homology 3 domain


SH2 domain-containing inositol 5-phosphatase-1


Surrogate light chain


Systemic lupus erythematosus


SH2 domain leukocyte protein of 65 kD


Spleen tyrosine kinase


Tyrosine kinase expressed in hepatocellular carcinoma

TH domain

TEC homology domain


Wiskott–Aldrich syndrome protein


Wild type


X-linked immunodeficiency


X-linked agammaglobulinemia



These studies were partly supported by the Dutch Arthritis Foundation and a VIRGO grant from the Dutch Organization for Scientific Research. We want to acknowledge Menno van Nimwegen, Marjolein de Bruijn, and Guus Rimmelzwaan (Erasmus MC) for their assistance.


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Authors and Affiliations

  • Odilia B. J. Corneth
    • 1
  • Roel G. J. Klein Wolterink
    • 1
  • Rudi W. Hendriks
    • 1
    Email author
  1. 1.Department of Pulmonary MedicineErasmus MC RotterdamRotterdamThe Netherlands

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