The 3BP2 Adapter Protein Is Required for Optimal B-Cell Activation and Thymus-Independent Type 2 Humoral Response
- 1 April 2007
- journal article
- research article
- Published by Taylor & Francis Ltd in Molecular and Cellular Biology
- Vol. 27 (8), 3109-3122
- https://doi.org/10.1128/mcb.01014-06
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.Keywords
This publication has 52 references indexed in Scilit:
- 3BP2 Deficiency Impairs the Response of B Cells, but Not T Cells, to Antigen Receptor LigationMolecular and Cellular Biology, 2006
- A gene atlas of the mouse and human protein-encoding transcriptomesProceedings of the National Academy of Sciences of the United States of America, 2004
- BTK Regulates PtdIns-4,5-P2 Synthesis: Importance for Calcium Signaling and PI3K ActivityImmunity, 2003
- DCs induce CD40-independent immunoglobulin class switching through BLyS and APRILNature Immunology, 2002
- Regulation of B Lymphocyte Responses to Foreign and Self-Antigens by the CD19/CD21 ComplexAnnual Review of Immunology, 2000
- Marginal zone B cells exhibit unique activation, proliferative and immunoglobulin secretory responsesEuropean Journal of Immunology, 1997
- Frequent Aberrant Immunoglobulin Gene Rearrangements in Pro-B Cells Revealed by a bcl-xL TransgeneImmunity, 1996
- Defective B cell development and function in Btk-deficient miceImmunity, 1995
- The CR2/CD19 complex on human B cells contains the src-family kinase LynInternational Immunology, 1993
- Identification of a Ten-Amino Acid Proline-Rich SH3 Binding SiteScience, 1993