The Journal of Immunology, Vol 158, Issue 7 3062-3069, Copyright © 1997 by American Association of Immunologists

ARTICLES

Membrane IgM-induced tyrosine phosphorylation of CD19 requires a CD19 domain that mediates association with components of the B cell antigen receptor complex

RH Carter, GM Doody, JB Bolen and DT Fearon
Department of Medicine, University of Alabama at Birmingham, 35294, USA.

CD19 enhances membrane IgM (mIgM) signaling and is required for B lymphocyte responses to T-dependent Ags. CD19 is tyrosine phosphorylated when mIgM is ligated and binds SH2 domain-containing signaling proteins. We suggest that the basis for phosphorylation is the association of CD19 with Syk and other components of the mIgM complex. IgM, CD22, Ig-alpha, Ig-beta, and Syk were coimmunoprecipitated with CD19 from detergent lysates of B lymphocytes. The association was maintained with a chimeric form of CD19 containing only the transmembrane domain and the membrane proximal 17 amino acids of the cytoplasmic domain encoded by exon 6. This sequence is sufficient to mediate the association, as a synthetic peptide of the exon 6-encoded region adsorbs IgM and Syk. Deletion of the juxtamembrane 17 amino acids of the cytoplasmic domain encoded by CD19 exon 6 abolishes association of CD19 with the mIgM complex. Deletion of these amino acids, which contain no tyrosines, also reduces mIgM- induced tyrosine phosphorylation of the remainder of the CD19 cytoplasmic domain. Coligating this mutant CD19 to mIgM restores phosphorylation. Thus, a discrete region of the cytoplasmic domain regulates the tyrosine phosphorylation of CD19 in the activation of B cells by mIgM.

This article has been cited by other articles:

				M. J. Polyak, H. Li, N. Shariat, and J. P. Deans CD20 Homo-oligomers Physically Associate with the B Cell Antigen Receptor: DISSOCIATION UPON RECEPTOR ENGAGEMENT AND RECRUITMENT OF PHOSPHOPROTEINS AND CALMODULIN-BINDING PROTEINS J. Biol. Chem., July 4, 2008; 283(27): 18545 - 18552. [Abstract] [Full Text] [PDF]

				L. Verkoczy, B. Duong, P. Skog, D. Ait-Azzouzene, K. Puri, J. L. Vela, and D. Nemazee Basal B Cell Receptor-Directed Phosphatidylinositol 3-Kinase Signaling Turns Off RAGs and Promotes B Cell-Positive Selection J. Immunol., May 15, 2007; 178(10): 6332 - 6341. [Abstract] [Full Text] [PDF]

				K. M. Haas, S. Sen, I. G. Sanford, A. S. Miller, J. C. Poe, and T. F. Tedder CD22 Ligand Binding Regulates Normal and Malignant B Lymphocyte Survival In Vivo. J. Immunol., September 1, 2006; 177(5): 3063 - 3073. [Abstract] [Full Text] [PDF]

				D. M. Mills, J. C. Stolpa, and J. C. Cambier Cognate B Cell Signaling via MHC Class II: Differential Regulation of B Cell Antigen Receptor and MHC Class II/Ig-{alpha}{beta} Signaling by CD22 J. Immunol., January 1, 2004; 172(1): 195 - 201. [Abstract] [Full Text] [PDF]

				P. K. A. Mongini, A. E. Jackson, S. Tolani, R. J. Fattah, and J. K. Inman Role of Complement-Binding CD21/CD19/CD81 in Enhancing Human B Cell Protection from Fas-Mediated Apoptosis J. Immunol., November 15, 2003; 171(10): 5244 - 5254. [Abstract] [Full Text] [PDF]

				C. H. Nielsen and R. G. Q. Leslie Complement's participation in acquired immunity J. Leukoc. Biol., August 1, 2002; 72(2): 249 - 261. [Abstract] [Full Text] [PDF]

				H. Phee, W. Rodgers, and K. M. Coggeshall Visualization of Negative Signaling in B Cells by Quantitative Confocal Microscopy Mol. Cell. Biol., December 15, 2001; 21(24): 8615 - 8625. [Abstract] [Full Text] [PDF]

				S. R. Brooks, X. Li, E. J. Volanakis, and R. H. Carter Systematic Analysis of the Role of CD19 Cytoplasmic Tyrosines in Enhancement of Activation in Daudi Human B Cells: Clustering of Phospholipase C and Vav and of Grb2 and Sos with Different CD19 Tyrosines J. Immunol., March 15, 2000; 164(6): 3123 - 3131. [Abstract] [Full Text] [PDF]

				L. O. Beitz, D. A. Fruman, T. Kurosaki, L. C. Cantley, and A. M. Scharenberg SYK Is Upstream of Phosphoinositide 3-Kinase in B Cell Receptor Signaling J. Biol. Chem., November 12, 1999; 274(46): 32662 - 32666. [Abstract] [Full Text] [PDF]

				M. Fujimoto, J. C. Poe, P. J. Jansen, S. Sato, and T. F. Tedder CD19 Amplifies B Lymphocyte Signal Transduction by Regulating Src-Family Protein Tyrosine Kinase Activation J. Immunol., June 15, 1999; 162(12): 7088 - 7094. [Abstract] [Full Text] [PDF]

				A. M. Buhl and J. C. Cambier Phosphorylation of CD19 Y484 and Y515, and Linked Activation of Phosphatidylinositol 3-Kinase, Are Required for B Cell Antigen Receptor-Mediated Activation of Bruton's Tyrosine Kinase J. Immunol., April 15, 1999; 162(8): 4438 - 4446. [Abstract] [Full Text] [PDF]

				T. Fehr, R. C. Rickert, B. Odermatt, J. Roes, K. Rajewsky, H. Hengartner, and R. M. Zinkernagel Antiviral Protection and Germinal Center Formation, But Impaired B Cell Memory in the Absence of CD19 J. Exp. Med., July 1, 1998; 188(1): 145 - 155. [Abstract] [Full Text] [PDF]

				A. M. Buhl, C. M. Pleiman, R. C. Rickert, and J. C. Cambier Qualitative Regulation of B Cell Antigen Receptor Signaling by CD19: Selective Requirement for PI3-Kinase Activation, Inositol-1,4,5-Trisphosphate Production and Ca2+ Mobilization J. Exp. Med., December 1, 1997; 186(11): 1897 - 1910. [Abstract] [Full Text] [PDF]

				D. C. Otero, S. A. Omori, and R. C. Rickert CD19-dependent Activation of Akt Kinase in B-lymphocytes J. Biol. Chem., January 5, 2001; 276(2): 1474 - 1478. [Abstract] [Full Text] [PDF]