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
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.