J. Exp. Med., Volume 187, Number 5, March 2, 1998 807-811

BRIEF DEFINITIVE REPORT:
Inhibition of the B Cell by CD22: A Requirement for Lyn

By Kenneth G.C. Smith,^* David M. Tarlinton, Gina M. Doody,^* Margaret L. Hibbs,^§ and Douglas T. Fearon^*

From the ^* Wellcome Trust Immunology Unit, Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge, England CB2 2SP; the  Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Parkville, Victoria 3050, Australia; and the ^§ Ludwig Institute for Cancer Research, Tumour Biology Branch, Royal Melbourne Hospital, Victoria 3050, Australia

Mice in which the Lyn, Cd22, or Shp-1 gene has been disrupted have hyperactive B cells and autoantibodies. We find that in the absence of Lyn, the ability of CD22 to become tyrosine phosphorylated after ligation of mIg, to recruit SHP-1, and to suppress mIg-induced elevation of intracellular [Ca²⁺] is lost. Therefore, Lyn is required for the SHP-1-mediated B cell suppressive function of CD22, accounting for similarities in the phenotypes of these mice.

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• HASLER, P., ZOUALI, M. (2001). B cell receptor signaling and autoimmunity. FASEB J. 15: 2085-2098 [Abstract] [Full Text]  
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• Ravetch, J. V., Lanier, L. L. (2000). Immune Inhibitory Receptors. Science 290: 84-89 [Abstract] [Full Text]  
• Ochi, H., Watanabe, T. (2000). Negative regulation of B cell receptor-mediated signaling in B-1 cells through CD5 and Ly49 co-receptors via Lyn kinase activity. Int Immunol 12: 1417-1423 [Abstract] [Full Text]  
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• Paul, S. P., Taylor, L. S., Stansbury, E. K., McVicar, D. W. (2000). Myeloid specific human CD33 is an inhibitory receptor with differential ITIM function in recruiting the phosphatases SHP-1 and SHP-2. Blood 96: 483-490 [Abstract] [Full Text]  
• Adachi, T., Wakabayashi, C., Nakayama, T., Yakura, H., Tsubata, T. (2000). CD72 Negatively Regulates Signaling Through the Antigen Receptor of B Cells. J. Immunol. 164: 1223-1229 [Abstract] [Full Text]  
• Xie, Z.-H., Zhang, J., Siraganian, R. P. (2000). Positive Regulation of c-Jun N-Terminal Kinase and TNF-{alpha} Production But Not Histamine Release by SHP-1 in RBL-2H3 Mast Cells. J. Immunol. 164: 1521-1528 [Abstract] [Full Text]  
• Gary-Gouy, H., Bruhns, P., Schmitt, C., Dalloul, A., Daeron, M., Bismuth, G. (2000). The Pseudo-immunoreceptor Tyrosine-based Activation Motif of CD5 Mediates Its Inhibitory Action on B-cell Receptor Signaling. J. Biol. Chem. 275: 548-556 [Abstract] [Full Text]  
• Carter, J. D., Neel, B. G., Lorenz, U. (1999). The tyrosine phosphatase SHP-1 influences thymocyte selection by setting TCR signaling thresholds. Int Immunol 11: 1999-2014 [Abstract] [Full Text]  
• Janas, M. L., Hodgkin, P., Hibbs, M., Tarlinton, D. (1999). Genetic Evidence for Lyn as a Negative Regulator of IL-4 Signaling. J. Immunol. 163: 4192-4198 [Abstract] [Full Text]  
• Lock, P., Casagranda, F., Dunn, A. R. (1999). Independent SH2-binding Sites Mediate Interaction of Dok-related Protein with RasGTPase-activating Protein and Nck. J. Biol. Chem. 274: 22775-22784 [Abstract] [Full Text]  
• Newton-Nash, D. K., Newman, P. J. (1999). A New Role for Platelet-Endothelial Cell Adhesion Molecule-1 (CD31): Inhibition of TCR-Mediated Signal Transduction. J. Immunol. 163: 682-688 [Abstract] [Full Text]  
• Fujimoto, M., Poe, J. C., Jansen, P. J., Sato, S., Tedder, T. F. (1999). CD19 Amplifies B Lymphocyte Signal Transduction by Regulating Src-Family Protein Tyrosine Kinase Activation. J. Immunol. 162: 7088-7094 [Abstract] [Full Text]  
• Li, H.-L., Davis, W. W., Whiteman, E. L., Birnbaum, M. J., Pure, E. (1999). The tyrosine kinases Syk and Lyn exert opposing effects on the activation of protein kinase Akt/PKB in B lymphocytes. Proc. Natl. Acad. Sci. USA 96: 6890-6895 [Abstract] [Full Text]  
• Greer, S. F., Justement, L. B. (1999). CD45 Regulates Tyrosine Phosphorylation of CD22 and Its Association with the Protein Tyrosine Phosphatase SHP-1. J. Immunol. 162: 5278-5286 [Abstract] [Full Text]  
• O'Keefe, T. L., Williams, G. T., Batista, F. D., Neuberger, M. S. (1999). Deficiency in CD22, a B Cell-specific Inhibitory Receptor, Is Sufficient to Predispose to Development of High Affinity Autoantibodies. J. Exp. Med. 189: 1307-1313 [Abstract] [Full Text]  
• Dong, Q., Siminovitch, K. A., Fialkow, L., Fukushima, T., Downey, G. P. (1999). Negative Regulation of Myeloid Cell Proliferation and Function by the SH2 Domain-Containing Tyrosine Phosphatase-1. J. Immunol. 162: 3220-3230 [Abstract] [Full Text]  
• Blasioli, J., Paust, S., Thomas, M. L. (1999). Definition of the Sites of Interaction between the Protein Tyrosine Phosphatase SHP-1 and CD22. J. Biol. Chem. 274: 2303-2307 [Abstract] [Full Text]  
• Theofilopoulos, A N (1998). Effector and predisposing genes in murine lupus. Lupus 7: 575-584 [Abstract]  
• Poe, J. C., Fujimoto, M., Jansen, P. J., Miller, A. S., Tedder, T. F. (2000). CD22 Forms a Quaternary Complex with SHIP, Grb2, and Shc. A PATHWAY FOR REGULATION OF B LYMPHOCYTE ANTIGEN RECEPTOR-INDUCED CALCIUM FLUX. J. Biol. Chem. 275: 17420-17427 [Abstract] [Full Text]  
• Somani, A.-K., Yuen, K., Xu, F., Zhang, J., Branch, D. R., Siminovitch, K. A. (2001). The SH2 Domain Containing Tyrosine Phosphatase-1 Down-regulates Activation of Lyn and Lyn-induced Tyrosine Phosphorylation of the CD19 Receptor in B Cells. J. Biol. Chem. 276: 1938-1944 [Abstract] [Full Text]  
• Adachi, T., Wienands, J., Wakabayashi, C., Yakura, H., Reth, M., Tsubata, T. (2001). SHP-1 Requires Inhibitory Co-receptors to Down-modulate B Cell Antigen Receptor-mediated Phosphorylation of Cellular Substrates. J. Biol. Chem. 276: 26648-26655 [Abstract] [Full Text]  
• Fujimoto, M., Poe, J. C., Hasegawa, M., Tedder, T. F. (2001). CD19 Amplification of B Lymphocyte Ca2+ Responses. A ROLE FOR Lyn SEQUESTRATION IN EXTINGUISHING NEGATIVE REGULATION. J. Biol. Chem. 276: 44820-44827 [Abstract] [Full Text]  
• Satterthwaite, A. B., Willis, F., Kanchanastit, P., Fruman, D., Cantley, L. C., Helgason, C. D., Humphries, R. K., Lowell, C. A., Simon, M., Leitges, M., Tarakhovsky, A., Tedder, T. F., Lesche, R., Wu, H., Witte, O. N. (2000). A sensitized genetic system for the analysis of murine B lymphocyte signal transduction pathways dependent on Bruton's tyrosine kinase. Proc. Natl. Acad. Sci. USA 97: 6687-6692 [Abstract] [Full Text]  
• Rudge, E. U., Cutler, A. J., Pritchard, N. R., Smith, K. G.C. (2002). Interleukin 4 Reduces Expression of Inhibitory Receptors on B Cells and Abolishes CD22 and Fc{gamma}RII-mediated B Cell Suppression. J. Exp. Med. 195: 1079-1085 [Abstract] [Full Text]  
• Kelm, S., Gerlach, J., Brossmer, R., Danzer, C.-P., Nitschke, L. (2002). The Ligand-binding Domain of CD22 Is Needed for Inhibition of the B Cell Receptor Signal, as Demonstrated by a Novel Human CD22-specific Inhibitor Compound. J. Exp. Med. 195: 1207-1213 [Abstract] [Full Text]  
• Jin, L., McLean, P. A., Neel, B. G., Wortis, H. H. (2002). Sialic Acid Binding Domains of CD22 Are Required For Negative Regulation of B Cell Receptor Signaling. J. Exp. Med. 195: 1199-1205 [Abstract] [Full Text]  

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