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Cutting Edge: Constitutive B Cell Receptor Signaling Is Critical for Basal Growth of B Lymphoma¹

Murali Gururajan^*,, C. Darrell Jennings^¶ and Subbarao Bondada^2,*,,,,¶

^* Department of Microbiology, Immunology and Molecular Genetics, Sanders Brown Center on Aging, University of Kentucky, Graduate Center for Toxicology, Markey Cancer Center, and ^¶ Pathology and Laboratory Medicine, University of Kentucky, Lexington, KY 40536

B lymphomas account for the majority of the lymphoma cases. BCR expression appears to be important for B lymphoma because most oncogenes are translocated to nonrearranged Ig loci and because all of the variants that arise in anti-idiotypic Ab-treated lymphoma patients remain BCR positive. Based on this and the fact that BCR is required for mature B cell survival, we tested the requirement for continued expression of BCR for the growth and survival of B lymphoma cells. Using Ig or Ig-specific small interfering RNA (siRNA) to inhibit BCR expression, we demonstrate for the first time that constitutive signaling by BCR is critical for survival and proliferation of both murine and human B lymphoma cells. The BCR signals in lymphoma appear to be mediated by Syk, as it is constitutively active in a variety of B lymphoma cells. Blocking Syk activity by selective inhibitors suppresses growth of several murine and human B lymphomas.

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