The B Cell Inhibitory Fc Receptor Triggers Apoptosis by a Novel c-Abl Family Kinase-dependent Pathway

• Published in: The Journal of biological chemistry 2005-10, Vol.280 (42), p.35247-35254
• Main Authors: Tzeng, Shiang-Jong, Bolland, Silvia, Inabe, Kazunori, Kurosaki, Tomohiro, Pierce, Susan K.
• Format: Article
• Language: English
• Subjects: Amino Acid Motifs; Animals; Antigens - chemistry; Antigens, CD - chemistry; Apoptosis; B-Lymphocytes - chemistry; B-Lymphocytes - immunology; Blotting, Western; Caspases - metabolism; Cell Cycle; Cell Line, Tumor; Chickens; Cytochromes c - metabolism; Cytoplasm - metabolism; DNA - chemistry; Hematopoietic Stem Cells - cytology; Immunoprecipitation; In Situ Nick-End Labeling; Membrane Potentials; Mice; Mitochondrial Membranes - metabolism; Phosphoric Monoester Hydrolases - chemistry; Phosphorylation; Protein-Tyrosine Kinases - metabolism; Proto-Oncogene Proteins c-abl - physiology; Receptors, Antigen, B-Cell - metabolism; Receptors, Fc - chemistry; Receptors, Fc - physiology; Receptors, IgG - chemistry; Signal Transduction
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M505308200

The inhibitory Fc receptors function to regulate the antigen-driven activation and expansion of lymphocytes. In B cells, the FcγRIIB1 is a potent inhibitor of B cell antigen receptor (BCR) signaling when coligated to the BCR by engagement of antigen-containing immune complexes. Inhibition is mediated by the recruitment of the inositol phosphatase, SHIP, to the FcγRIIB1 phosphorylated tyrosine-based inhibitory motif (ITIM). Here we show that BCR-independent aggregation of the FcγRIIB1 transduces an ITIM- and SHIP-independent proapoptotic signal that is dependent on members of the c-Abl tyrosine kinase family. These results define a novel Abl family kinase-dependent FcγRIIB1 signaling pathway that functions independently of the BCR in controlling antigen-driven B cell responses.