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Cutting Edge: Inherent and Acquired Resistance to Radiation-Induced Apoptosis in B Cells: A Pivotal Role for STAT3¹

Dennis C. Otero^*, Valeria Poli, Michael David^* and Robert C. Rickert^2,

^* Division of Biological Sciences and University of California San Diego Moore’s Cancer Center, University of California, San Diego, La Jolla, CA 92093; Department of Genetics, Biology, and Biochemistry, University of Turin, Turin, Italy; and Burnham Institute for Medical Research, La Jolla, CA 92037

Radiation-induced apoptosis (RiA) is used therapeutically for tumor cell ablation as well as a tool to characterize hemopoietic cell lineages. We report that the peritoneal B-1 B cell subset is selectively resistant to RiA. Inherent radioresistance is not shared by splenic B-2 or B-1 cells. However, it is conferred upon B-2 cells by BCR crosslinking in the presence of IL-6 or IL-10. In vivo experiments with gene-targeted mice confirm that IL-6 and, to a lesser extent, IL-10 are the relevant stimuli that combine with BCR ligands to promote B-1 cell radioresistance. STAT3 promotes cell survival in response to selected growth factors, and is activated by combined BCR crosslinking and IL-6 (IL-10). Importantly, STAT3^–/– B-1 cells become susceptible to irradiation, indicating that STAT3 activation by the BCR in the presence of IL costimuli account for the inherent radioresistance of peritoneal B-1 B cells.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by an American Cancer Society Research Scholar Award (to R.C.R.), a Concern Foundation Junior Faculty Award (to R.C.R.), an Italian Cancer Research Association (AIRC) grant (to V.P.), and National Institutes of Health Grant NCI-CA80105 (to M.D.). D.C.O. is supported by National Institutes of Health Training Grant T32 CA09523.

² Address correspondence and reprint requests to Dr. Robert C. Rickert, Burnham Institute for Medical Research, 10901 N. Torrey Pines Road, La Jolla, CA 92037. E-mail address: robert{at}burnham.org

³ Abbreviations used in this paper: PeC, peritoneal cavity; RiA, radiation-induced apoptosis; HSC, hematopoietic stem cell; PI, propidium iodide; WT, wild type.

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