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Blood, 15 May 2004, Vol. 103, No. 10, pp. 3828-3836. Prepublished online as a Blood First Edition Paper on February 12, 2004February 24, 2004; DOI 10.1182/blood-2003-10-3470. This Article Full Text (PDF) Supplemental Figures All Versions of this Article: 2003-10-3470v1 2003-10-3470v2 103/10/3828    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 Khamlichi, A. A Articles by Cogne, M. Search for Related Content PubMed PubMed Citation Articles by Khamlichi, A. A Articles by Cogne, M. Social Bookmarking                   What's this? Submitted October 10, 2003 Accepted December 31, 2003 Immunoglobulin class switch recombination in mice devoid of any Sµ tandem repeat Ahmed A Khamlichi*, Florence Glaudet, Zeliha Oruc, Vincent Denis, Marc Le Bert, and Michel Cogne Immunology, CNRS UMR 6101, Limoges, France CDTA, CNRS UPS 44, Orleans, France * Corresponding author; email: khamlich{at}unilim.fr. Immunoglobulin heavy chain class switch recombination (CSR) occurs between highly repetitive switch sequences located upstream of the constant region genes. However, the role of these sequences remains unclear. Mutant mice were generated in which most of the Iµ-Cµ intron was deleted including all the repeats. Late B cell development was characterized by a severe impairment, but not a complete block, in class switching to all isotypes despite normal germline transcription. Sequence analysis of the Iµ-Cµ intron in in vitro activated-mutant splenocytes did not reveal any significant increase in AID-induced somatic mutations. Analysis of switch junctions showed that, in the absence of any Sµ repeat, the Iµ exon was readily used as a substrate for CSR. In contrast to the sequence alterations downstream of the switch junctions, very few, if any, mutations were found upstream of the junction sites. Our data suggest that the core Eµ enhancer could be the boundary for CSR-associated somatic mutations. We propose that the core Eµ enhancer plays a central role in the temporal dissociation of somatic hypermutation from class switching. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: L. Wang, R. Wuerffel, S. Feldman, A. A. Khamlichi, and A. L. Kenter S region sequence, RNA polymerase II, and histone modifications create chromatin accessibility during class switch recombination J. Exp. Med., August 3, 2009; 206(8): 1817 - 1830. [Abstract] [Full Text] [PDF] D. Rajagopal, R. W. Maul, A. Ghosh, T. Chakraborty, A. A. Khamlichi, R. Sen, and P. J. Gearhart Immunoglobulin switch {micro} sequence causes RNA polymerase II accumulation and reduces dA hypermutation J. Exp. Med., June 8, 2009; 206(6): 1237 - 1244. [Abstract] [Full Text] [PDF] U. Basu, A. Franklin, and F. W Alt Post-translational regulation of activation-induced cytidine deaminase Phil Trans R Soc B, March 12, 2009; 364(1517): 667 - 673. [Abstract] [Full Text] [PDF] A. Arudchandran, R. M. Bernstein, and E. E. Max Single-strand DNA breaks in Ig class switch recombination that depend on UNG but not AID Int. Immunol., November 1, 2008; 20(11): 1381 - 1393. [Abstract] [Full Text] [PDF] A. A. Zarrin, P. H. Goff, K. Senger, and F. W. Alt S{gamma}3 switch sequences function in place of endogenous S{gamma}1 to mediate antibody class switching J. Exp. Med., July 7, 2008; 205(7): 1567 - 1572. [Abstract] [Full Text] [PDF] Z. Oruc, A. Boumediene, M. Le Bert, and A. A. Khamlichi Replacement of I{gamma}3 germ-line promoter by I{gamma}1 inhibits class-switch recombination to IgG3 PNAS, December 18, 2007; 104(51): 20484 - 20489. [Abstract] [Full Text] [PDF] F.-T. Huang, K. Yu, B. B. Balter, E. Selsing, Z. Oruc, A. A. Khamlichi, C.-L. Hsieh, and M. R. Lieber Sequence Dependence of Chromosomal R-Loops at the Immunoglobulin Heavy-Chain S{micro} Class Switch Region Mol. Cell. Biol., August 15, 2007; 27(16): 5921 - 5932. [Abstract] [Full Text] [PDF] A. A. Zarrin, C. Del Vecchio, E. Tseng, M. Gleason, P. Zarin, M. Tian, and F. W. Alt Antibody Class Switching Mediated by Yeast Endonuclease-Generated DNA Breaks Science, January 19, 2007; 315(5810): 377 - 381. [Abstract] [Full Text] [PDF] M. Samara, Z. Oruc, H.-L. Dougier, T. Essawi, M. Cogne, and A. A. Khamlichi Germ line transcription in mice bearing neor gene downstream of I{gamma}3 exon in the Ig heavy chain locus Int. Immunol., April 1, 2006; 18(4): 581 - 589. [Abstract] [Full Text] [PDF] K. Wakae, B. G. Magor, H. Saunders, H. Nagaoka, A. Kawamura, K. Kinoshita, T. Honjo, and M. Muramatsu Evolution of class switch recombination function in fish activation-induced cytidine deaminase, AID Int. Immunol., January 1, 2006; 18(1): 41 - 47. [Abstract] [Full Text] [PDF] I. M. Min, L. R. Rothlein, C. E. Schrader, J. Stavnezer, and E. Selsing Shifts in targeting of class switch recombination sites in mice that lack {micro} switch region tandem repeats or Msh2 J. Exp. Med., June 20, 2005; 201(12): 1885 - 1890. [Abstract] [Full Text] [PDF] A. A. Zarrin, M. Tian, J. Wang, T. Borjeson, and F. W. Alt Influence of switch region length on immunoglobulin class switch recombination PNAS, February 15, 2005; 102(7): 2466 - 2470. [Abstract] [Full Text] [PDF]

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