The 3BP2 adapter protein is required for optimal B-cell activation and thymus-independent type 2 humoral response.
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.
Chen
Grace
G
Princess Margaret Hospital/Ontario Cancer Institute, Room 10-105, University Ave., Toronto, ON, Canada.
Dimitriou
Ioannis D
ID
La Rose
Jose
J
Ilangumaran
Subburaj
S
Yeh
Wen-Chen
WC
Doody
Gina
G
Turner
Martin
M
Gommerman
Jennifer
J
Rottapel
Robert
R
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*
D048868:Adaptor Proteins, Signal Transducing; D018956:CD5 Antigens; D012333:RNA, Messenger; C484644:Sh3bp2 protein, mouse