The B cell inhibitory Fc receptor triggers apoptosis by a novel c-Abl family kinase-dependent pathway.
The inhibitory Fc receptors function to regulate the antigen-driven activation and expansion of lymphocytes. In B cells, the Fc gammaRIIB1 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 Fc gammaRIIB1 phosphorylated tyrosine-based inhibitory motif (ITIM). Here we show that BCR-independent aggregation of the Fc gammaRIIB1 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 Fc gammaRIIB1 signaling pathway that functions independently of the BCR in controlling antigen-driven B cell responses.
Tzeng
Shiang-Jong
SJ
Laboratory of Immunogenetics, NIAID, National Institutes of Health, Rockville, Maryland 20852, USA.
Bolland
Silvia
S
Inabe
Kazunori
K
Kurosaki
Tomohiro
T
Pierce
Susan K
SK
D020816:Amino Acid Motifs; D000818:Animals; D000941:Antigens / Q000737:chemistry; D015703:Antigens, CD / Q000737:chemistry; D017209:Apoptosis; D001402:B-Lymphocytes / Q000737:chemistry / Q000276:immunology*; D015153:Blotting, Western; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle; D045744:Cell Line, Tumor; D002645:Chickens; D045304:Cytochromes c / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004247:DNA / Q000737:chemistry; D006412:Hematopoietic Stem Cells / Q000166:cytology; D047468:Immunoprecipitation; D020287:In Situ Nick-End Labeling; D008564:Membrane Potentials; D051379:Mice; D051336:Mitochondrial Membranes / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000737:chemistry; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D016315:Proto-Oncogene Proteins c-abl / Q000502:physiology*; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D011961:Receptors, Fc / Q000737:chemistry / Q000502:physiology*; D017452:Receptors, IgG / Q000737:chemistry; D015398:Signal Transduction
D000941:Antigens; D015703:Antigens, CD; C080571:Fc gamma receptor IIB; D011947:Receptors, Antigen, B-Cell; D011961:Receptors, Fc; D017452:Receptors, IgG; D045304:Cytochromes c; D004247:DNA; D011505:Protein-Tyrosine Kinases; D016315:Proto-Oncogene Proteins c-abl; D010744:Phosphoric Monoester Hydrolases; C021822:myo-inositol-1 (or 4)-monophosphatase; D020169:Caspases