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International Immunology Advance Access published online on January 13, 2006
International Immunology, 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
Received April 26, 2005
Accepted November 29, 2005

Article

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

Sonia Néron 1, Garnet Suck 2, Xue-Zhong Ma 2, Darinka Sakac 2, Annie Roy 3, Yulia Katsman 2, Nathalie Dussault 3, Claudia Racine 3, and Donald R. Branch 4 *

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

* To whom correspondence should be addressed.
Donald R. Branch, E-mail: don.branch{at}utoronto.ca


  Abstract

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.
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