Recently, immunoglobulins (Igs) were unexpectedly found to be expressed in epithelial cancers. Immunoglobulin class switching or class switch recombination (CSR) is a natural biological process that alters a B cell’s production of antibodies (immunoglobulins) from one class to another. However, the mechanism of CSR of Ig genes in cancer is still unknown. Here, we confirmed by detecting the hallmark of CSR that the Igα gene in cancer underwent CSR. Then we focused on activation-induced cytidine deaminase (AID), a crucial factor for initiating CSR. Further studies using tumor necrosis factor (TNF)-α stimulation and specific inhibitor of NF-κB revealed that TNF-α could increase AID expression through NF-κB signaling. Finally, we demonstrated that AID could co-localize with protein kinase A and bind to the switching (Sα) region of the Igα gene. Overexpression of AID obviously enhanced Igα heavy chain expression and its binding ability to the Sα region. These findings indicated that TNF-α-induced AID expression is involved with CSR in cancer.
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We thank Professor Gu Jiang (Department of Pathology, Shantou University Medical College, Shantou, China) for providing the HeLa S3 cell line. We also thank Professor Songqing Fan (The Second Xiangya Hospital, Central South University, Changsha, China) for quantifying the immunohistochemistry results.
This work was supported by the National High Technology Research and Development Program (863) of China (No. 2006AA02A404) and the National Nature Science Foundation of China (No. 30772465, No. 30973399).
The authors declare no financial or commercial conflict of interest.
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Duan, Z., Zheng, H., Liu, H. et al. AID expression increased by TNF-α is associated with class switch recombination of Igα gene in cancers. Cell Mol Immunol 13, 484–491 (2016). https://doi.org/10.1038/cmi.2015.26