The Journal of Immunology, 2004, 172: 2727.
Copyright © 2004 by The American Association of Immunologists
Lack of Association between Human Switch Recombination Breakpoints and the Secondary Structure of Targeted DNA Regions
Qiang Pan-Hammarström,
Yaofeng Zhao and
Lennart Hammarström
Division of Clinical Immunology, Department of Laboratory Medicine, Karolinska Institutet at Huddinge Hospital, Stockholm, Sweden
Center for Biotechnology, NOVUM, Huddinge, Sweden
As class switch recombination (CSR) is a region, rather than a site-specific event, a relationship between the recombination breakpoints and the structural character of the switch (S) regions involved has been sought. It has earlier been suggested that CSR preferentially occurs at transitions from a stem to a loop structure in ssDNA (microsites) in S regions from a variety of species (1, 2). However, only a limited number of breakpoints have been analyzed (1, 2). In the October 1, 2003 issue of The Journal of Immunology, Cameron et al. (3) showed that three of the four breakpoints described (Sµ, S
, and S
) from nasal tissue also mapped to microsites and suggested that their observations represented the first evidence for a structural recognition pattern in primary human B cells. However, we have previously shown, using a large number of S
breakpoints from in vivo switched human B cells, that the percentage of breakpoints at microsites is not higher than expected by chance (4). We have now reanalyzed our previously published S
breakpoints (n = 68) and added another 130 Sµ and 62 S
breakpoints, using the standard applied by Tashiro et al. (2). As shown in Table I, the percentage of breakpoints at microsites is not higher than expected by chance (
2 test), even though many S junctions are indeed located at (position 0), or in the proximity of (position 1), these sites (for full data see www.biosci.ki.se/users/qipa/microsites). Therefore, new ways of exploring the role of secondary and tertiary structure of the S regions are required to explain the location of the switch recombination breakpoints.
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Table I. Occurrence of breakpoints in the proximity of the transitions from stem-to-loop regions in the secondary structure (microsites) in human S regionsa
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References
- Mussmann, R., M. Courtet, J. Schwager, L. Du Pasquier. 1997. Microsites for immunoglobulin switch recombination breakpoints from Xenopus to mammals. Eur. J. Immunol. 27:2610.[Medline]
- Tashiro, J., K. Kinoshita, T. Honjo. 2001. Palindromic but not G-rich sequences are targets of class switch recombination. Int. Immunol. 13:495.[Abstract/Free Full Text]
- Cameron, L., A. S. Gounni, S. Frenkiel, F. Lavigne, D. Vercelli, Q. Hamid. 2003. S
Sµ and S
S
switch circles in human nasal mucosa following ex vivo allergen challenge: evidence for direct as well as sequential class switch recombination. J. Immunol. 171:3816.[Abstract/Free Full Text]
- Pan, Q., L. Hammarström. 2000. Molecular basis of IgG subclass deficiency. Immunol. Rev. 178:99.[Medline]