Cutting edge: inherent and acquired resistance to radiation-induced apoptosis in B cells: a pivotal role for STAT3.
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.
Otero
Dennis C
DC
Division of Biological Sciences and University of California San Diego Moore's Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA.
Poli
Valeria
V
David
Michael
M
Rickert
Robert C
RC
D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000528:radiation effects*; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000528:radiation effects*; D002478:Cells, Cultured; D005720:Gamma Rays; D007113:Immunity, Innate / Q000235:genetics / Q000528:radiation effects; D016753:Interleukin-10 / Q000502:physiology; D015850:Interleukin-6 / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010529:Peritoneal Cavity / Q000166:cytology / Q000528:radiation effects; D010766:Phosphorylation; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism / Q000502:physiology; D050796:STAT3 Transcription Factor / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D012694:Serine / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology / Q000528:radiation effects
D015850:Interleukin-6; D011947:Receptors, Antigen, B-Cell; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D016753:Interleukin-10; D012694:Serine