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Cutting Edge |
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* Graduate Program in Immunology, Departments of
Microbiology, and
Internal Medicine, and
Veterans Affairs Medical Center, University of Iowa, Iowa City, IA 52242
Optimal Ag-specific B lymphocyte activation requires both recognition of Ag by the B cell Ag receptor (BCR) and contact-mediated interactions with Ag-specific Th lymphocytes. One of these interactions involves ligation of B cell CD40 by T cell-expressed CD154. CD40 signaling is crucial for Ab production, isotype switching, up-regulation of surface molecules, development of germinal centers, and the humoral memory response. The signaling pathways emanating from the BCR and CD40 are able to cooperate, but the molecular mechanisms responsible for this interaction are incompletely understood. The present study explored the roles of signaling motifs in the CD40 cytoplasmic tail in this synergy. We find that threonine in the PXQXT motif in the TNFR-associated factor-2 binding site is critical for synergistic effects of CD40 and BCR signals, independent of its phosphorylation. Furthermore, data suggest an indirect role for TNFR-associated factor-2 in the cooperative signaling.
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C. R. Moore and G. A. Bishop Differential Regulation of CD40-Mediated TNF Receptor-Associated Factor Degradation in B Lymphocytes J. Immunol., September 15, 2005; 175(6): 3780 - 3789. [Abstract] [Full Text] [PDF]
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Q. Li, A. C. Grover, E. J. Donald, A. Carr, J. Yu, J. Whitfield, M. Nelson, N. Takeshita, and A. E. Chang Simultaneous Targeting of CD3 on T Cells and CD40 on B or Dendritic Cells Augments the Antitumor Reactivity of Tumor-Primed Lymph Node Cells J. Immunol., August 1, 2005; 175(3): 1424 - 1432. [Abstract] [Full Text] [PDF]
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 J. Hauer, S. Puschner, P. Ramakrishnan, U. Simon, M. Bongers, C. Federle, and H. Engelmann TNF receptor (TNFR)-associated factor (TRAF) 3 serves as an inhibitor of TRAF2/5-mediated activation of the noncanonical NF-{kappa}B pathway by TRAF-binding TNFRs PNAS, February 22, 2005; 102(8): 2874 - 2879. [Abstract] [Full Text] [PDF]
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C. M. Grimaldi, R. Hicks, and B. Diamond B Cell Selection and Susceptibility to Autoimmunity J. Immunol., February 15, 2005; 174(4): 1775 - 1781. [Abstract] [Full Text] [PDF]
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M. E. Munroe and G. A. Bishop Role of Tumor Necrosis Factor (TNF) Receptor-associated Factor 2 (TRAF2) in Distinct and Overlapping CD40 and TNF Receptor 2/CD120b-mediated B Lymphocyte Activation J. Biol. Chem., December 17, 2004; 279(51): 53222 - 53231. [Abstract] [Full Text] [PDF]
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P. Xie and G. A. Bishop Roles of TNF Receptor-Associated Factor 3 in Signaling to B Lymphocytes by Carboxyl-Terminal Activating Regions 1 and 2 of the EBV-Encoded Oncoprotein Latent Membrane Protein 1 J. Immunol., November 1, 2004; 173(9): 5546 - 5555. [Abstract] [Full Text] [PDF]
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G. Liao, M. Zhang, E. W. Harhaj, and S.-C. Sun Regulation of the NF-{kappa}B-inducing Kinase by Tumor Necrosis Factor Receptor-associated Factor 3-induced Degradation J. Biol. Chem., June 18, 2004; 279(25): 26243 - 26250. [Abstract] [Full Text] [PDF]
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S. A. Haxhinasto and G. A. Bishop Synergistic B Cell Activation by CD40 and the B Cell Antigen Receptor: ROLE OF B LYMPHOCYTE ANTIGEN RECEPTOR-MEDIATED KINASE ACTIVATION AND TUMOR NECROSIS FACTOR RECEPTOR-ASSOCIATED FACTOR REGULATION J. Biol. Chem., January 23, 2004; 279(4): 2575 - 2582. [Abstract] [Full Text] [PDF]
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B. S. Hostager, S. A. Haxhinasto, S. L. Rowland, and G. A. Bishop Tumor Necrosis Factor Receptor-associated Factor 2 (TRAF2)-deficient B Lymphocytes Reveal Novel Roles for TRAF2 in CD40 Signaling J. Biol. Chem., November 14, 2003; 278(46): 45382 - 45390. [Abstract] [Full Text] [PDF]
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L.-F. Lu, W. J. Cook, L.-L. Lin, and R. J. Noelle CD40 Signaling through a Newly Identified Tumor Necrosis Factor Receptor-associated Factor 2 (TRAF2) Binding Site J. Biol. Chem., November 14, 2003; 278(46): 45414 - 45418. [Abstract] [Full Text] [PDF]
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S. A. Haxhinasto and G. A. Bishop A Novel Interaction between Protein Kinase D and TNF Receptor-Associated Factor Molecules Regulates B Cell Receptor-CD40 Synergy J. Immunol., November 1, 2003; 171(9): 4655 - 4662. [Abstract] [Full Text] [PDF]
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