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Estrogen up-regulates Bcl-2 and blocks tolerance induction of naïve B cells
Open accessAbstract
Sex hormones are presumed to contribute to sexual dimorphism in the immune system. Estrogen, in particular, has been suggested to predispose women to systemic lupus erythematosus. We report here that estradiol (E 2) can break B cell tolerance and induce a lupus-like phenotype in nonautoimmune mice transgenic for the heavy chain of a pathogenic anti-DNA antibody. E 2 treatment resulted in a rise in anti-DNA serum titers and in Ig deposition in renal glomeruli. ELISPOT analysis confirmed a significant increase in the number of high-affinity anti-DNA antibody-secreting B cells in the spleens of E 2-treated mice. Hybridomas generated from E 2-treated mice express high-affinity, unmutated anti-DNA antibodies, indicating that naïve B cells that are normally deleted or anergized are rescued from tolerance induction. Finally, immunohistochemical studies revealed increased Bcl-2 expression in splenic B cells of E 2-treated mice. These data demonstrate that estrogen interferes with tolerance induction of naïve autoreactive B cells and that the presence of these B cells in the periphery is associated with up-regulation of Bcl-2.
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Cited by
Chen, J.-Q., Cammarata, P. R., Baines, C. P., & Yager, J. D. (2009) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2009.06.001 · Cited by 264
Gender differences in skin: A review of the literature
Dao, H., & Kazin, R. A. (2007) · Gender Medicine · doi:10.1016/s1550-8579(07)80061-1 · Cited by 199
DIFFERENT ROLES FOR ANDROGENS AND ESTROGENS IN THE SUSCEPTIBILITY TO AUTOIMMUNE RHEUMATIC DISEASES
Cutolo, M., & Wilder, R. L. (2000) · Rheumatic Disease Clinics of North America · doi:10.1016/s0889-857x(05)70171-x · Cited by 176
Increase in multiple sclerosis activity after assisted reproduction technology
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Metadata
- Authors
- Bynoe, M. S., Grimaldi, C. M., & Diamond, B.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2000-02-29
- Volume
- 97
- Issue
- 6
- Pages
- 2703-2708
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2019743324
- Cited by
- 274
- References
- 0
- FWCI
- 8.16
- Type
- journal article
- Language
- en
- Open access
- green
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- Bynoe, M. S., Grimaldi, C. M., & Diamond, B. (2000). Estrogen up-regulates Bcl-2 and blocks tolerance induction of naïve B cells. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.040577497
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