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The Journal of Immunology, Vol 158, Issue 12 5849-5859, Copyright © 1997 by American Association of Immunologists
ARTICLES |
Q Pan, H Rabbani, FC Mills, E Severinson and L Hammarstrom
Department of Clinical Immunology and Center for BioTechnology, NOVUM Karolinska Institute at Huddinge Hospital, Sweden. qiang.pan@csb.ki.se
High and low serum concentrations of IgG3 are associated with the human G3 m(b) and G3 m(g) allotypes, respectively. We previously hypothesized that a low frequency of switching is the most likely defect in (g) allotype-positive individuals, and therefore analyzed the structure, recombination breakpoints, and binding of nuclear proteins to the switch (S)gamma3 regions of these two allotypes. There are no allotype- associated differences in the length and basic structure of the Sgamma3, since both contain eighteen 79-bp repeats. However, we found a number of allotype-associated nucleotide changes. As in the mouse system, there is a preferential switching to the B site, or switch nuclear protein/nuclear factor-kappaB motif, with a clustering of switch breakpoints at the most 5' residue of the B site. The B site sequence used most frequently in switching was found to be mutated at this nucleotide in the (g) allotype-associated Sgamma3. This change was shown by electrophoretic mobility shift assay to alter the binding of the switch nuclear protein/nuclear factor-kappaB protein to the B site. Taken together, these data suggest that polymorphism within Sgamma3 may contribute to allotype-associated differences in IgG3 switching, and that specific sequences within the Sgamma3 79-bp repeats could be mechanistically important for switch recombination.
This article has been cited by other articles:
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  Q. Pan-Hammarstrom, A. Lahdesmaki, Y. Zhao, L. Du, Z. Zhao, S. Wen, V. L. Ruiz-Perez, D. K. Dunn-Walters, J. A. Goodship, and L. Hammarstrom Disparate roles of ATR and ATM in immunoglobulin class switch recombination and somatic hypermutation J. Exp. Med., January 23, 2006; 203(1): 99 - 110. [Abstract] [Full Text] [PDF]
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Q. Pan-Hammarstrom, A.-M. Jones, A. Lahdesmaki, W. Zhou, R. A. Gatti, L. Hammarstrom, A. R. Gennery, and M. R. Ehrenstein Impact of DNA ligase IV on nonhomologous end joining pathways during class switch recombination in human cells J. Exp. Med., January 18, 2005; 201(2): 189 - 194. [Abstract] [Full Text] [PDF]
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 Y. Zhao, Q. Pan-Hammarstrom, Z. Zhao, S. Wen, and L. Hammarstrom Selective IgG2 deficiency due to a point mutation causing abnormal splicing of the C{gamma}2 gene Int. Immunol., January 1, 2005; 17(1): 95 - 101. [Abstract] [Full Text] [PDF]
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 A. Lahdesmaki, A. M. R. Taylor, K. H. Chrzanowska, and Q. Pan-Hammarstrom Delineation of the Role of the Mre11 Complex in Class Switch Recombination J. Biol. Chem., April 16, 2004; 279(16): 16479 - 16487. [Abstract] [Full Text] [PDF]
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 Q. Pan-Hammarstrom, S. Dai, Y. Zhao, I. F. van Dijk-Hard, R. A. Gatti, A.-L. Borresen-Dale, and L. Hammarstrom ATM Is Not Required in Somatic Hypermutation of VH, but Is Involved in the Introduction of Mutations in the Switch {micro} Region J. Immunol., April 1, 2003; 170(7): 3707 - 3716. [Abstract] [Full Text] [PDF]
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Q. Pan, H. Rabbani, and L. Hammarstrom Characterization of Human {gamma}4 Switch Region Polymorphisms Suggests a Meiotic Recombinational Hot Spot Within the Ig Locus: Influence of S Region Length on IgG4 Production J. Immunol., October 1, 1998; 161(7): 3520 - 3526. [Abstract] [Full Text] [PDF]
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