Tyrosine kinase activation in the decision between growth, differentiation, and death responses initiated from the B cell antigen receptor.
Immunoglobulin-containing receptors expressed on B lineage lymphocytes play critical roles in the development and function of the humoral arm of the immune system. The preB cell antigen receptor (preBCR) contains the immunoglobulin mu heavy chain (Ig mu) and signals to the preB cell that heavy chain rearrangement has been successful, a process termed heavy chain selection. The B cell antigen receptor (BCR) contains both Ig heavy and light chains and is expressed on immature and mature B cells before and after antigen encounter. Both receptor types from a complex with the Ig alpha and Ig beta proteins that link the predominantly extracellular Ig with intracellular signal transduction pathways. Signaling through the BCR induces different cellular responses depending on the nature of the signaling agent and the development stage of the target cell. These responses include clonal anergy and apoptotic deletion in immature B cells and survival, proliferation, and differentiation in mature B and preB cells. Several protein tyrosine kinases are activated rapidly following engagement of the BCR/preBCR complexes, including members of the Src family (Lyn and Blk), the Syk/ZAP70 family (Syk), and the Tec family (Btk). In this review, we discuss possible mechanisms by which engagement of these similar receptor complexes can give rise to different cellular responses and the role that these kinases play in this process.
Hsueh
R C
RC
Laboratory of Molecular Pathology, University of Texas Southwestern Medical Center, Dallas 75235, USA.
Scheuermann
R H
RH
D000077329:Agammaglobulinaemia Tyrosine Kinase; D000917:Antibody Formation; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D017209:Apoptosis / Q000502:physiology*; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000201:enzymology* / Q000276:immunology; D051925:CD79 Antigens; D002454:Cell Differentiation / Q000502:physiology*; D002455:Cell Division / Q000502:physiology*; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000502:physiology; D005803:Genes, Immunoglobulin; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007153:Immunologic Deficiency Syndromes / Q000201:enzymology / Q000235:genetics / Q000276:immunology; D047908:Intracellular Signaling Peptides and Proteins; D008213:Lymphocyte Activation; D010766:Phosphorylation; D010950:Plasma Cells / Q000166:cytology / Q000276:immunology; D011499:Protein Processing, Post-Translational; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D011947:Receptors, Antigen, B-Cell / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000276:immunology; D015398:Signal Transduction; D000072377:Syk Kinase; D051746:ZAP-70 Protein-Tyrosine Kinase; D018909:src Homology Domains; D019061:src-Family Kinases / Q000172:deficiency / Q000235:genetics / Q000502:physiology
D015703:Antigens, CD; D051925:CD79 Antigens; C497881:CD79A protein, human; C497883:CD79B protein, human; D004792:Enzyme Precursors; D007143:Immunoglobulin Heavy Chains; D047908:Intracellular Signaling Peptides and Proteins; D011947:Receptors, Antigen, B-Cell; D011993:Recombinant Fusion Proteins; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human; C000606896:SYK protein, human; D000072377:Syk Kinase; D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human; D019061:src-Family Kinases