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Evolution of Autoantibody Responses via Somatic Hypermutation Outside of Germinal Centers
Abstract
Somatically mutated high-affinity autoantibodies are a hallmark of some autoimmune diseases, including systemic lupus erythematosus. It has long been presumed that germinal centers (GCs) are critical in autoantibody production, because they are the only sites currently believed to sustain a high rate of somatic hypermutation. Contrary to this idea, we found that splenic autoreactive B cells in autoimmune MRL.Fas lpr mice proliferated and underwent active somatic hypermutation at the T zone–red pulp border rather than in GCs. Our results implicate this region as an important site for hypermutation and the loss of B cell self-tolerance.
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Citations
Cited by
Chiorazzi, N., Rai, K. R., & Ferrarini, M. (2005) · New England Journal of Medicine · doi:10.1056/nejmra041720 · Cited by 1,296
Jenks, S. A., Cashman, K. S., Zumaquero, E., Marigorta, U. M., Patel, A. V., Wang, X., Tomar, D., Woodruff, M. C., Simon, Z., Bugrovsky, R., et al. (2018) · Immunity · doi:10.1016/j.immuni.2018.08.015 · Cited by 1,078
Extrafollicular B cell responses correlate with neutralizing antibodies and morbidity in COVID-19
Woodruff, M. C., Ramonell, R. P., Nguyen, D. C., Cashman, K. S., Saini, A. S., Haddad, N. S., Ley, A. M., Kyu, S., Howell, J. C., Ozturk, T., et al. (2020) · Nature Immunology · doi:10.1038/s41590-020-00814-z · Cited by 791
Germinal Center and Extrafollicular B Cell Responses in Vaccination, Immunity, and Autoimmunity
Elsner, R. A., & Shlomchik, M. J. (2020) · Immunity · doi:10.1016/j.immuni.2020.11.006 · Cited by 526
Self-citationPillai, S., Cariappa, A., & Moran, S. T. (2005) · Annual Review of Immunology · doi:10.1146/annurev.immunol.23.021704.115728 · Cited by 466
Metadata
- Authors
- William, J., Euler, C., Christensen, S., & Shlomchik, M. J.
- Venue
- Science
- Published
- 2002-09-20
- Volume
- 297
- Issue
- 5589
- Pages
- 2066-2070
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2014523162
- Cited by
- 559
- References
- 0
- FWCI
- 17.50
- Type
- journal article
- Language
- en
- Open access
- closed
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- William, J., Euler, C., Christensen, S., & Shlomchik, M. J. (2002). Evolution of Autoantibody Responses via Somatic Hypermutation Outside of Germinal Centers. Science. https://doi.org/10.1126/science.1073924
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
