SHIP recruitment attenuates Fc gamma RIIB-induced B cell apoptosis.
Fc gammaRIIB is an inhibitory receptor that terminates activation signals initiated by antigen cross-linking of the BCR through the recruitment of SHIP. Fc gammaRIIB can also signal independently of BCR coligation to directly mediate an apoptotic response, requiring only an intact transmembrane domain. Failure to recruit SHIP, either by deletion of SHIP or mutation of Fc gammaRIIB, results in enhanced Fc gammaRIIB-triggered apoptosis. Thus, in the germinal center, where ICs are retained by FDCs, Fc gammaRIIB may be an active determinant in the negative selection of B cells whose BCRs have reduced affinity for antigen as a result of somatic hypermutation. Selection of B cells may represent the sum of opposing signals generated by the interaction of ICs with the BCR and Fc gammaRIIB through pathways modulated by SHIP.
Laboratory of Molecular Genetics and Immunology, The Rockefeller University, New York, New York 10021, USA.
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Pearse
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Kawabe
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Bolland
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Guinamard
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Kurosaki
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Ravetch
D000077329:Agammaglobulinaemia Tyrosine Kinase; D000818:Animals; D000936:Antigen-Antibody Complex / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology / Q000502:physiology*; D017209:Apoptosis / Q000276:immunology*; D001402:B-Lymphocytes / Q000166:cytology* / Q000378:metabolism*; D002645:Chickens; D003713:Dendritic Cells / Q000276:immunology; D051379:Mice; D008954:Models, Biological; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism* / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis / Q000502:physiology; D011947:Receptors, Antigen, B-Cell / Q000502:physiology; D017452:Receptors, IgG / Q000276:immunology / Q000502:physiology*; D013154:Spleen / Q000166:cytology / Q000502:physiology
D000936:Antigen-Antibody Complex; D015703:Antigens, CD; C080571:Fc gamma receptor IIB; D011947:Receptors, Antigen, B-Cell; D017452:Receptors, IgG; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; D010744:Phosphoric Monoester Hydrolases; C098706:INPPL1 protein, human; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases