Negative regulator of B cell function

Bruton's tyrosine kinase (Btk) critical for lymphocyte B cell survival but if unchecked, can result in immunodeficiency of the development of cancer. In October Nature Immunology, Weimin Liu and colleagues from University of Catanzaro, Italy report the identification of a new Btk-interacting protein — IBtk — that inhibits the activity of Btk in B cells.

Working with yeast plasmids and T cells, Liu et al. identified IBtk, a molecule that inhibits Btk by binding to the PH domain of the protein. In addition, they found that IBtk downregulates Btk kinase activity, Btk-mediated calcium mobilization and nuclear factor-κB–driven transcription (Nat Immunol 2001, 2:939-946).

The authors suggests that the discovery of IBtk may lead to a better understanding of the clinical heterogeneity in human X-linked agammaglobulinemia, which is characterized by genetic mutations in the Btk-PH domain.