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Blood, 15 May 2006, Vol. 107, No. 10, pp. 3967-3975. Prepublished online as a Blood First Edition Paper on January 31, 2006January 26, 2006; DOI 10.1182/blood-2005-10-4170. This Article Full Text (PDF) All Versions of this Article: 2005-10-4170v1 2005-10-4170v2 107/10/3967    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 Cattoretti, G. Articles by Niedobitek, G. Search for Related Content PubMed PubMed Citation Articles by Cattoretti, G. Articles by Niedobitek, G. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted October 20, 2005 Accepted January 7, 2006 Nuclear and cytoplasmic AID in extrafollicular and Germinal Center B cells Giorgio Cattoretti*, Maike Buttner, Rita Shaknovich, Elisabeth Kremmer, Bachir Alobeid, and Gerald Niedobitek Institute for Cancer Genetics, Columbia University, New York, NY, USA; Department of Pathology, Columbia University Medical Center, New York, NY, USA Institute for Pathology, Friedrich-Alexander-University, Erlangen, Germany Department of Pathology, Albert Einstein College of Medicine, New York, NY, USA Institute of Molecular Immunology, GSF-National Research Center for Environment and Health, Munchen, Germany Department of Pathology, Columbia University Medical Center, New York, NY, USA * Corresponding author; email: gc87{at}columbia.edu. Activation Induced Cytidine Deaminase (AID) is necessary for immunoglobulin somatic hypermutation (SHM) and class switch recombination (CSR) in T-dependent immune response in Germinal Centers (GC). The structural similarity with RNA-editing enzymes and its largely cytoplasmic location has fueled controversial views of its mode of interaction with the DNA. We show that AID, a mature B cell restricted cytoplasmic antigen, is relocated into the nucleus in 2.5% of CDKN1B-, CCNB1- GC cells. The GC dark zone and the outer zone (OZ) contain nuclear and cytoplasmic AID+ blasts, but not the light zone. AID+ cells in the OZ are in contact with T cells and CD23-negative follicular dendritic cells. In addition, AID is expressed in extrafollicular large proliferating B cells, 14% of them have nuclear AID. GC and extrafollicular AID+ cells express E47 but not the inhibiting BHLH protein Id2. Outside the GC, AID+ B cells are in contact with T cells, show partial evidence of CD40+bcr stimulation-dependent signature (CCL22, JunB, cMYC, CD30) but lack early and late plasma cell markers. The distribution of nuclear AID is consistent with the topography of SHM and CSR inside the GC and in extrafollicular activated B cells. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: N. S. Longo, P. L. Lugar, S. Yavuz, W. Zhang, P. H. L. Krijger, D. E. Russ, D. D. Jima, S. S. Dave, A. C. Grammer, and P. E. Lipsky Analysis of somatic hypermutation in X-linked hyper-IgM syndrome shows specific deficiencies in mutational targeting Blood, April 16, 2009; 113(16): 3706 - 3715. [Abstract] [Full Text] [PDF] A. Bagg Malleable Immunoglobulin Genes and Hematopathology - The Good, the Bad, and the Ugly: A Paper from the 2007 William Beaumont Hospital Symposium on Molecular Pathology J. Mol. 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