Signal transduction elements of the B cell antigen receptor and their role in immunodeficiencies.

The primary function of B lymphocytes is to contribute to the elimination of foreign antigens by producing large amounts of soluble antibodies. The activation of B cells through their antigen receptor triggers a dynamic network of intracellular signaling proteins. The recent identification of the cytoplasmic adaptor protein SLP-65 (also called BLNK or BASH) provided insight in how the antigen receptor-regulated protein tyrosine kinases couple to downstream signaling cascades, including the mobilization of Ca2+ ions, activation of mitogen-activated kinases and reorganization of the cytoskeleton architecture. While these events have been mostly studied in mature B cells, it is now clear that the components of the antigen receptor and its downstream effector elements play also a central role during early and late B cell development, and in the apoptotic elimination of B cells with reactivity to self-antigens. Thus, genetic defects affecting the expression of antigen receptor subunits or its intracellular signaling proteins can interfere with B cell development and activation, and can cause severe antibody deficiencies in mouse and man. In this article I summarize our current picture of the B cell antigen receptor, how the extracellular signal is transported into the cell interior, and how dysregulation of these processes contribute to immune defects.