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.
Wienands
J
J
Institute of Biology III, University of Freiburg and Max-Planck-Institute of Immunobiology, Germany. wienands@immunbio.mpg.de
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D004789:Enzyme Activation; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000276:immunology*; D015398:Signal Transduction; D013379:Substrate Specificity; D048051:p38 Mitogen-Activated Protein Kinases
D048868:Adaptor Proteins, Signal Transducing; C113939:B cell linker protein; D002352:Carrier Proteins; D010750:Phosphoproteins; D011947:Receptors, Antigen, B-Cell; D011505:Protein-Tyrosine Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D002118:Calcium