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International Immunology Advance Access originally published online on January 13, 2006
International Immunology 2006 18(2):375-387; doi:10.1093/intimm/dxh377
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© The Japanese Society for Immunology. 2006. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

B cell proliferation following CD40 stimulation results in the expression and activation of Src protein tyrosine kinase

Sonia Néron1,2, Garnet Suck3, Xue-Zhong Ma3, Darinka Sakac3, Annie Roy1, Yulia Katsman3, Nathalie Dussault1, Claudia Racine1 and Donald R. Branch3,4

1 Héma-Québec, Recherche et Développement, Sainte-Foy, Québec, Canada
2 Département de Biochimie et Microbiologie, Université Laval, Québec, Canada
3 Research and Development, Canadian Blood Services, 67 College Street, Toronto, Ontario, M5G 2M1, Canada
4 Division of Cell and Molecular Biology, Toronto General Research Institute, Toronto, Ontario, Canada

Correspondence to: D. R. Branch; E-mail: don.branch{at}utoronto.ca or S. Néron; E-mail: sonia.neron{at}hema-quebec.qc.ca

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.

Keywords: CD40–CD154, cell signaling, lymphomas, oncogenes, tyrosine phosphorylation

Transmitting editor: C. J. Paige


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