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Identification of a specific self-reactive IgM antibody that initiates intestinal ischemia/reperfusion injury
Open accessAbstract
Reperfusion injury of ischemic tissue represents an acute inflammatory response that can cause significant morbidity and mortality. The mechanism of injury is not fully elucidated, but recent studies indicate an important role for natural antibody and the classical pathway of complement. To test the hypothesis that injury is initiated by specific IgM, we have screened a panel of IgM-producing hybridomas prepared from peritoneal cells enriched in B-1 cells. One clone, CM22, was identified that could restore pathogenic injury in RAG-1 -/- mice in an intestinal model of ischemia/reperfusion (I/R). In situ activation of the classical pathway of complement was evident by deposition of IgM, complement C4, and C3 in damaged tissue after passive transfer of CM22 IgM. Sequence analysis of CM22 Ig heavy and light chains showed germ-line configurations with high homology to a V H sequence from the B-1 repertoire and a V K of a known polyreactive natural IgM. These data provide definitive evidence that I/R injury can be initiated by clonally specific natural IgM that activates the classical pathway of complement. This finding opens an avenue for identification of I/R-specific self-antigen(s) and early prevention of injury.
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Citations
Cited by
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Rock, K. L., & Kono, H. (2008) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev.pathmechdis.3.121806.151456 · Cited by 912
Zouggari, Y., Ait-Oufella, H., Bonnin, P., Simon, T., Sage, A. P., Guérin, C., Vilar, J., Caligiuri, G., Tsiantoulas, D., Laurans, L., et al. (2013) · Nature Medicine · doi:10.1038/nm.3284 · Cited by 559
HARBOE, M., ULVUND, G., VIEN, L., FUNG, M., & MOLLNES, T. E. (2004) · Clinical and Experimental Immunology · doi:10.1111/j.1365-2249.2004.02627.x · Cited by 319
Plasma cell development and survival
Oracki, S. A., Walker, J. A., Hibbs, M. L., Corcoran, L. M., & Tarlinton, D. M. (2010) · Immunological Reviews · doi:10.1111/j.1600-065x.2010.00940.x · Cited by 268
Metadata
- Authors
- Zhang, M., Austen, W. G., Chiu, I., Alicot, E. M., Hung, R., Ma, M., Verna, N., Xu, M., Hechtman, H. B., Moore, F. D., & Carroll, M. C.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2004-03-03
- Volume
- 101
- Issue
- 11
- Pages
- 3886-3891
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2146388575
- Cited by
- 215
- References
- 0
- FWCI
- 5.45
- Type
- journal article
- Language
- en
- Open access
- green
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- Zhang, M., Austen, W. G., Chiu, I., Alicot, E. M., Hung, R., Ma, M., Verna, N., Xu, M., Hechtman, H. B., Moore, F. D., & Carroll, M. C. (2004). Identification of a specific self-reactive IgM antibody that initiates intestinal ischemia/reperfusion injury. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0400347101
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