title: The 3BP2 adapter protein is required for optimal B-cell activation and thymus-independent type 2 humoral response.
abstract: 3BP2 is a pleckstrin homology domain- and Src homology 2 (SH2) domain-containing adapter protein that is mutated in the rare human bone disorder cherubism and which has also been implicated in immunoreceptor signaling. However, a function for this protein has yet to be established. Here we show that mice lacking 3BP2 exhibited a perturbation in the peritoneal B1 and splenic marginal-zone B-cell compartments and diminished thymus-independent type 2 antigen response. 3BP2(-/-) B cells demonstrated a proliferation defect in response to antigen receptor cross-linking and a heightened sensitivity to B-cell receptor-induced death via a caspase-3-dependent apoptotic pathway. We show that 3BP2 binds via its SH2 domain to the CD19 signaling complex and is required for optimum Syk phosphorylation and calcium flux.
authors.affiliation: Princess Margaret Hospital/Ontario Cancer Institute, Room 10-105, University Ave., Toronto, ON, Canada.
authors.forename: Grace
authors.initials: G
authors.lastname: Chen
authors.forename: Ioannis D
authors.initials: ID
authors.lastname: Dimitriou
authors.forename: Jose
authors.initials: J
authors.lastname: La Rose
authors.forename: Subburaj
authors.initials: S
authors.lastname: Ilangumaran
authors.forename: Wen-Chen
authors.initials: WC
authors.lastname: Yeh
authors.forename: Gina
authors.initials: G
authors.lastname: Doody
authors.forename: Martin
authors.initials: M
authors.lastname: Turner
authors.forename: Jennifer
authors.initials: J
authors.lastname: Gommerman
authors.forename: Robert
authors.initials: R
authors.lastname: Rottapel
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000917:Antibody Formation / Q000276:immunology*; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D018956:CD5 Antigens / Q000276:immunology; D002452:Cell Count; D002460:Cell Line; D049109:Cell Proliferation; D002470:Cell Survival; D005786:Gene Expression Regulation; D006801:Humans; D007114:Immunization; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010537:Peritoneum / Q000166:cytology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013154:Spleen / Q000166:cytology; D013950:Thymus Gland / Q000276:immunology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018956:CD5 Antigens; D012333:RNA, Messenger; C484644:Sh3bp2 protein, mouse