SEARCH:   Advanced

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 (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 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 Related Articles in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted March 19, 2008 Accepted June 29, 2008 Alternative splicing regulates activation-induced cytidine deaminase (AID): Implications for suppression of AID mutagenic activity in normal and malignant B-cells Xiaosheng Wu, Jaime R Darce, Sook Kyung Chang, Grzegorz S Nowakowski, and Diane F Jelinek* Department of Immunology, Mayo Clinic, Rochester, MN, United States Department of Medicine, Mayo Clinic, Rochester, MN, United States * Corresponding author; email: jelinek.diane{at}mayo.edu. The mutagenic enzyme activation-induced cytidine deaminase (AID) is absolutely 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. Importantly, 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 B-cell 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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Articles in Blood Online: Response: P-selectin ready for the "News at Six" Cihan Ay and Ingrid Pabinger Blood 2009 113: 1860-1861. [Full Text] [PDF] Insurance policies in the United States may explain part of the outcome differences of adolescents and young adults with acute lymphoblastic leukemia treated on adult versus pediatric regimens Hagop M. Kantarjian and Susan O'Brien Blood 2009 113: 1861. [Full Text] [PDF] Response: Disparity in outcome of young adults with ALL Wendy Stock Blood 2009 113: 1862. [Full Text] [PDF] AID splice variants lack deaminase activity Febe van Maldegem, Ferenc A. Scheeren, R. Aarti Jibodh, Richard J. Bende, Heinz Jacobs, and Carel J. M. van Noesel Blood 2009 113: 1862-1864. [Full Text] [PDF] Response: Cautious interpretation of assessment of AID variant activities using cells with endogenous AID expression Xiaosheng Wu and Diane F. Jelinek Blood 2009 113: 1864. [Full Text] [PDF] C/EBPA methylation is common in T-ALL but not in M0 AML Louis Terriou, Raouf Ben Abdelali, Christophe Roumier, Ludovic Lhermitte, John de Vos, Pascale Cornillet, Olivier Nibourel, Kheira Beldjord, Hervé Dombret, Guy Leverger, Vahid Asnafi, Claude Preudhomme, and Elizabeth Macintyre Blood 2009 113: 1864-1866. [Full Text] [PDF] Response: CEBPA promoter hypermethylation in a subset of myeloid/T-lymphoid leukemias with a distinct gene expression profile Bas Wouters and Ruud Delwel Blood 2009 113: 1866. [Full Text] [PDF] JAK2-V617F–triggered preemptive and salvage adoptive immunotherapy with donor-lymphocyte infusion in patients with myelofibrosis after allogeneic stem cell transplantation Nicolaus Kröger, Haefaa Alchalby, Evgeny Klyuchnikov, Anita Badbaran, York Hildebrandt, Francis Ayuk, Ulrike Bacher, Oliver Bock, Michael Kvasnicka, Boris Fehse, and Axel Zander Blood 2009 113: 1866-1868. [Full Text] [PDF] Older age does not influence allogeneic peripheral blood stem cell mobilization in a donor population of mostly white ethnic origin Hugues de Lavallade, Patrick Ladaique, Claude Lemarié, Sabine Fürst, Catherine Faucher, Didier Blaise, Christian Chabannon, and Boris Calmels Blood 2009 113: 1868-1869. [Full Text] [PDF] This article has been cited by other articles: X. Wu and D. F. Jelinek Response: Cautious interpretation of assessment of AID variant activities using cells with endogenous AID expression Blood, February 19, 2009; 113(8): 1864 - 1864. [Full Text] [PDF] F. van Maldegem, F. A. Scheeren, R. Aarti Jibodh, R. J. Bende, H. Jacobs, and C. J. M. van Noesel AID splice variants lack deaminase activity Blood, February 19, 2009; 113(8): 1862 - 1864. [Full Text] [PDF] S. Pauklin, I. V. Sernandez, G. Bachmann, A. R. Ramiro, and S. K. Petersen-Mahrt Estrogen directly activates AID transcription and function J. Exp. Med., January 16, 2009; 206(1): 99 - 111. [Abstract] [Full Text] [PDF]

	Copyright © 2008 by American Society of Hematology         Online ISSN: 1528-0020