SEARCH:   Advanced

Blood, 16 April 2009, Vol. 113, No. 16, pp. 3706-3715. Prepublished online as a Blood First Edition Paper on November 20, 2008; DOI 10.1182/blood-2008-10-183632. This Article Full Text Full Text (PDF) Supplemental Tables and Figures All Versions of this Article: blood-2008-10-183632v1 113/16/3706    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 Longo, N. S. Articles by Lipsky, P. E. Search for Related Content PubMed PubMed Citation Articles by Longo, N. S. Articles by Lipsky, P. E. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Analysis of somatic hypermutation in X-linked hyper-IgM syndrome shows specific deficiencies in mutational targeting Nancy S. Longo1, Patricia L. Lugar1, Sule Yavuz1, Wen Zhang1, Peter H. L. Krijger1, Daniel E. Russ2, Dereje D. Jima3, Sandeep S. Dave3,4, Amrie C. Grammer1, and Peter E. Lipsky1 1 Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, and 2 Division of Computational Bioscience, Center for Information Technology, National Institutes of Health, Bethesda, MD; 3 Duke Institute for Genome Sciences and Policy, Duke University, Durham, NC; and 4 Department of Medicine, Duke University Medical Center, Durham, NC Subjects with X-linked hyper-IgM syndrome (X-HIgM) have a markedly reduced frequency of CD27+ memory B cells, and their Ig genes have a low level of somatic hypermutation (SHM). To analyze the nature of SHM in X-HIgM, we sequenced 209 nonproductive and 926 productive Ig heavy chain genes. In nonproductive rearrangements that were not subjected to selection, as well as productive rearrangements, most of the mutations were within targeted RGYW, WRCY, WA, or TW motifs (R = purine, Y = pyrimidine, and W = A or T). However, there was significantly decreased targeting of the hypermutable G in RGYW motifs. Moreover, the ratio of transitions to transversions was markedly increased compared with normal. Microarray analysis documented that specific genes involved in SHM, including activation-induced cytidine deaminase (AICDA) and uracil-DNA glycosylase (UNG2), were up-regulated in normal germinal center (GC) B cells, but not induced by CD40 ligation. Similar results were obtained from light chain rearrangements. These results indicate that in the absence of CD40-CD154 interactions, there is a marked reduction in SHM and, specifically, mutations of AICDA-targeted G residues in RGYW motifs along with a decrease in transversions normally related to UNG2 activity. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. Kuraoka, D. Liao, K. Yang, S. D. Allgood, M. C. Levesque, G. Kelsoe, and Y. Ueda Activation-Induced Cytidine Deaminase Expression and Activity in the Absence of Germinal Centers: Insights into Hyper-IgM Syndrome J. Immunol., September 1, 2009; 183(5): 3237 - 3248. [Abstract] [Full Text] [PDF]

	Copyright © 2009 by American Society of Hematology         Online ISSN: 1528-0020