Genetic analysis of B cell antigen receptor signaling.
In B lymphocytes, a signaling complex that contributes to cell fate decisions is the B cell antigen receptor (BCR). Data from knockout experiments in cell lines and mice have revealed distinct functions for the intracellular protein tyrosine kinases (Lyn, Syk, Btk) in BCR signaling and B cell development. Combinations of intracellular signaling pathways downstream of these PTKs determine the quality and quantity of BCR signaling. For example, concerted actions of the PLC-gamma 2 and PI3-K pathways are required for proper calcium responses. Similarly, the regulation of ERK and JNK responses involves both PLC-gamma 2 and GTPases pathways. Since the immune response in vivo is regulated by alteration of these signaling outcomes, achieving a precise understanding of intracellular molecular events leading to B lymphocyte proliferation, deletion, anergy, receptor editing, and survival still remains a challenge for the future.
Kurosaki
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Department of Molecular Genetics, Kansai Medical University, Moriguchi, Japan. kurosaki@mxr.meshnet.or.jp
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation; D019204:GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D050356:Lipid Metabolism; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000235:genetics*; D015398:Signal Transduction
D011947:Receptors, Antigen, B-Cell; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; D017027:Protein Tyrosine Phosphatases; D019204:GTP-Binding Proteins