B cell proliferation following CD40 stimulation results in the expression and activation of Src protein tyrosine kinase.
Resting normal human B cells express negligible c-src mRNA or Src protein tyrosine kinase; however, upon induction of proliferation, these cells express high levels of both mRNA and protein and show a concomitant increase in tyrosine kinase activity of immunoprecipitated Src. Src expression was most pronounced upon stimulation with CD154, and to a lesser extent CD70, Staphylococcus aureus, Cowan strain I and phorbol ester, and correlated with the activation of the cells. Transfection of cDNA for human wild-type or kinase-dead Src into Raji B cells resulted in an increase and decrease, respectively, of the cell numbers in culture, showing a direct correlation of proliferation to the expression of Src that was corroborated using anti-sense oligodeoxynucleotides and chemical inhibitors. Furthermore, the human B cell lines, Namalwa, Daudi and Raji express low levels of Src but express very high levels of Src after stimulation with CD154 that showed a correlation with increased activation. This is the first report of Src detectable in normal B cells. The finding that Src expression is inducible and correlates with stimulation by CD154 and the proliferation of the B cells suggests that Src may play a specific role in normal and transformed B cell activation/proliferation pathways mediated primarily through CD40 stimulation.
Néron
Sonia
S
Héma-Québec, Recherche et Développement, Sainte-Foy, Québec, Canada. sonia.neron@hema-quebec.qc.ca
Suck
Garnet
G
Ma
Xue-Zhong
XZ
Sakac
Darinka
D
Roy
Annie
A
Katsman
Yulia
Y
Dussault
Nathalie
N
Racine
Claudia
C
Branch
Donald R
DR
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000201:enzymology*; D019013:CD40 Antigens / Q000502:physiology*; D002460:Cell Line; D049109:Cell Proliferation; D004789:Enzyme Activation; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D051379:Mice; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology; D019061:src-Family Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
C412373:AG 1879; D019013:CD40 Antigens; D007211:Indoles; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; C416927:SU 6656; D013449:Sulfonamides; D019061:src-Family Kinases