First published June 2, 2014 - More info
The IL-12Rβ2 gene is expressed in human mature B cell subsets but not in transformed B cell lines. Silencing of this gene may be advantageous to neoplastic B cells. Our objective was to investigate the mechanism(s) and the functional consequence(s) of IL-12Rβ2 gene silencing in primary B cell tumors and transformed B cell lines. Purified tumor cells from 41 patients with different chronic B cell lymphoproliferative disorders, representing the counterparts of the major mature human B cell subsets, tested negative for IL-12Rβ2 gene expression. Hypermethylation of a CpG island in the noncoding exon 1 was associated with silencing of this gene in malignant B cells. Treatment with the DNA methyltransferase inhibitor 5-Aza-2′-deoxycytidine restored IL-12Rβ2 mRNA expression in primary neoplastic B cells that underwent apoptosis following exposure to human recombinant IL-12 (hrIL-12). hrIL-12 inhibited proliferation and increased the apoptotic rate of IL-12Rβ2–transfected B cell lines in vitro. Finally, hrIL-12 strongly reduced the tumorigenicity of IL-12Rβ2–transfected Burkitt lymphoma RAJI cells in SCID-NOD mice through antiproliferative and proapoptotic effects, coupled with neoangiogenesis inhibition related to human IFN-γ–independent induction of hMig/CXCL9. The IL-12Rβ2 gene acts as tumor suppressor in chronic B cell malignancies, and IL-12 exerts direct antitumor effects on IL-12Rβ2–expressing neoplastic B cells.
Irma Airoldi, Emma Di Carlo, Barbara Banelli, Lidia Moserle, Claudia Cocco, Annalisa Pezzolo, Carlo Sorrentino, Edoardo Rossi, Massimo Romani, Alberto Amadori, Vito Pistoia
Original citation: J. Clin. Invest. 2004;113(11):1651–1659. doi:10.1172/JCI20303.
Citation for this retraction: J. Clin. Invest. 2014;124(6):2807. doi:10.1172/JCI76855.
It has come to our attention that multiple gel images in Figure 1A were inappropriately duplicated from a previous publication (Airoldi I. et al. Expression and function of IL-12 and IL-18 receptors on human tonsillar B cells. J Immunol. 2000;165(12):6880–6888) in violation of JCI editorial policy. The experimental results presented in Figure 1A were intentionally mislabeled as representing total tonsil B lymphocytes and naive, GC, and memory B cells from the same tonsil, in contrast with the sample labeling in the previous publication. The JCI editorial board is retracting this article due to the evident misrepresentation of data and image duplication. No issues have been raised in regard to any of the other data in this manuscript.