CD19 amplifies B lymphocyte signal transduction by regulating Src-family protein tyrosine kinase activation

Citation
M. Fujimoto et al., CD19 amplifies B lymphocyte signal transduction by regulating Src-family protein tyrosine kinase activation, J IMMUNOL, 162(12), 1999, pp. 7088-7094
Citations number
42
Categorie Soggetti
Immunology
Journal title
JOURNAL OF IMMUNOLOGY
ISSN journal
00221767 → ACNP
Volume
162
Issue
12
Year of publication
1999
Pages
7088 - 7094
Database
ISI
SICI code
0022-1767(19990615)162:12<7088:CABLST>2.0.ZU;2-4
Abstract
Ligation of the B cell kg receptor (BCR) in;luces cellular activation by st imulating Src-family protein tyrosine kinases (PTKs) to phosphorylate membe rs of the BCR complex. Subsequently, Src-family PTKs, particularly Lyn, are proposed to phosphorylate and bind CD19, a cell-surface costimulatory mole cule that regulates mature B cell activation, Herein, we show that B cells from CD19-deficient mice have diminished Lyn kinase activity and BCR phosph orylation following BCR ligation, Tyrosine phosphorylation of other Src-fam ily PTKs was also decreased in CD19-deficient B cells. In wild-type B cells , CD19 was constitutively complexed with Vav, Lyn, and other Src-family PTK s, with CD19 phosphorylation and its associations with Lyn and Vav increase d after BCR ligation, Constitutive CD19/Lyn/Vav complex signaling may there fore be responsible for the establishment of baseline signaling thresholds in B cells before Ag receptor ligation, in addition,to accelerating signali ng following BCR engagement or other transmembrane signals. In vitro kinase assays using purified CD19 and purified Lyn revealed that the kinase activ ity of Lyn was significantly increased when coincubated with CD19; Thus, co nstitutive and induced CD19/Lyn complexes are likely to regulate basal sign aling thresholds and BCR signaling by amplifying the kinase activity of Lyn and other Src-family PTKs, These in. vivo and in vitro-findings demonstrat e a novel mechanism by which CD19-regulates signal transduction in B lympho cytes, The absence of this CD19/Src-family kinase amplification loop may ac count for the hyporesponsive phenotype of CD19-deficient B cells.