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Blood, 1 December 2008, Vol. 112, No. 12, pp. 4675-4682. Prepublished online as a Blood First Edition Paper on August 6, 2008; DOI 10.1182/blood-2008-03-145995. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2008-03-145995v1 112/12/4675    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Wu, X. Articles by Jelinek, D. F. Search for Related Content PubMed PubMed Citation Articles by Wu, X. Articles by Jelinek, D. F. Related Collections Neoplasia Related Articles in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Alternative splicing regulates activation-induced cytidine deaminase (AID): implications for suppression of AID mutagenic activity in normal and malignant B cells Xiaosheng Wu1, Jaime R. Darce1, Sook Kyung Chang1, Grzegorz S. Nowakowski2, and Diane F. Jelinek1 1 Department of Immunology and 2 Department of Medicine, College of Medicine, Mayo Clinic, Rochester, MN The mutagenic enzyme activation-induced cytidine deaminase (AID) is required for immunoglobulin class switch recombination (CSR) and somatic hypermutation (SHM) in germinal center (GC) B cells. Deregulated expression of AID is associated with various B-cell malignancies and, currently, it remains unclear how AID activity is extinguished to avoid illegitimate mutations. AID has also been shown to be alternatively spliced in malignant B cells, and there is limited evidence that this also occurs in normal blood B cells. The functional significance of these splice variants remains unknown. Here we show that normal GC human B cells and blood memory B cells similarly express AID splice variants and show for the first time that AID splicing variants are singly expressed in individual normal B cells as well as malignant B cells from chronic lymphocytic leukemia patients. We further demonstrate that the alternative AID splice variants display different activities ranging from inactivation of CSR to inactivation or heightened SHM activity. Our data therefore suggest that CSR and SHM are differentially switched off by varying the expression of splicing products of AID at the individual cell level. Most importantly, our findings suggest a novel tumor suppression mechanism by which unnecessary AID mutagenic activities are promptly contained for GC B cells. 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