Functions of Bruton's tyrosine kinase in mast and B cells

Bruton's tyrosine kinase (Btk) plays crucial roles in B cell differentiation as well as mast cell activation through the high‐affinity IgE receptor (Fc∊RI). Defects in the btk gene lead to agammaglobulinemia ( XLA ) in humans and X‐linked immunodeficiency ( xid ) in mice. Mast cells from xid and btk null mice exhibit mild defects in degranulation and severe impairments in the production of proinflammatory cytokines upon Fc∊RI cross‐linking. Recent studies demonstrated the role of Btk in a sustained increase in intracellular calcium concentrations in response to antigen receptor stimulation. Btk is also involved in the activation of stress‐activated protein kinases, JNK/SAPK1/2, and thereby regulates c‐Jun and other transcription factors that are important in cytokine gene activation. Regulation of the JNK/SAPK activation pathway by Btk may be related to the proapoptotic function of Btk in the programmed cell death in these hematopoietic cells. J. Leukoc. Biol. 65: 286–290; 1999.