Estrogen can modulate autoimmunity in certain models of systemic lupus erythematosus. Recently, we have shown that it can mediate survival and activation of anti-DNA B cells in a mouse transgenic for the heavy chain of a pathogenic anti-DNA antibody. To identify whether estrogen effects reflect increased prolactin secretion, we characterized B-cell autoreactivity in transgenic mice given both bromocriptine (an inhibitor of prolactin secretion) and estradiol. Treatment of mice with estradiol plus bromocriptine led to reduced titers of anti-DNA antibodies and diminished IgG deposition in kidneys compared with treatment with estradiol alone. However, mice treated with estradiol plus bromocriptine showed an expansion of transgene-expressing B cells and enhanced Bcl-2 expression, similar to those of estradiol-treated mice. We identified anergic high-affinity anti-DNA B cells in mice treated with estradiol plus bromocriptine, and we showed by molecular analysis of anti-DNA hybridomas that their B cells derive from a naive repertoire. Thus, the estradiol-induced breakdown in B-cell tolerance can be abrogated by bromocriptine, which induces anergy in the high-affinity DNA-reactive B cells. These studies demonstrate that some of the effects of estrogen on naive autoreactive B cells require the presence of prolactin and, thus, suggest potential therapeutic interventions in lupus.
Elena Peeva, Christine Grimaldi, Linda Spatz, Betty Diamond
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Hormones and B-cell development in health and autoimmunity
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Abnormally high expression of D1-like dopamine receptors on lupus CD4+ T cells promotes Tfh cell differentiation
Wu F, Xiang Z, He Z, Yi P, Yang M, Wu H, Hu M |
Lupus Science & Medicine | 2023 |
Peripheral Dopamine Controlled by Gut Microbes Inhibits Invariant Natural Killer T Cell-Mediated Hepatitis
R Xue, H Zhang, J Pan, Z Du, W Zhou, Z Zhang, Z Tian, R Zhou, L Bai |
Frontiers in immunology | 2018 |
Prolactin has a pathogenic role in systemic lupus erythematosus
LJ Jara, G Medina, MA Saavedra, O Vera-Lastra, H Torres-Aguilar, C Navarro, MV Mercado, LR Espinoza |
Immunologic Research | 2017 |
The Effects of Bromocriptine on Preventing Postpartum Flare in Systemic Lupus Erythematosus Patients from South China
Q Qian, L Liuqin, L Hao, Y Shiwen, Z Zhongping, C Dongying, L Fan, X Hanshi, Y Xiuyan, Y Yujin |
Journal of Immunology Research | 2015 |
The Dopaminergic System in Autoimmune Diseases
R Pacheco, F Contreras, M Zouali |
Frontiers in immunology | 2014 |
Prolactin rescues and primes autoreactive B cells directly and indirectly through dendritic cells in B6.Sle3 mice
J Gonzalez, S Saha, E Peeva |
Clinical & Experimental Immunology | 2013 |
Prolactin and Autoimmunity: Hyperprolactinemia Correlates with Serositis and Anemia in SLE Patients
H Orbach, G Zandman-Goddard, M Boaz, N Agmon-Levin, H Amital, Z Szekanecz, G Szucs, J Rovensky, E Kiss, A Doria, A Ghirardello, J Gomez-Arbesu, L Stojanovich, F Ingegnoli, PL Meroni, B Rozman, M Blank, Y Shoenfeld |
Clinical Reviews in Allergy & Immunology | 2011 |
PD-1, gender, and autoimmunity
RK Dinesh, BH Hahn, RP Singh |
Autoimmunity Reviews | 2010 |
The Unexplained Female Predominance of Systemic Lupus Erythematosus: Clues from Genetic and Cytokine Studies
CE Weckerle, TB Niewold |
Clinical Reviews in Allergy & Immunology | 2010 |
The Multi-faceted Influences of Estrogen on Lymphocytes: Toward Novel Immuno-interventions Strategies for Autoimmunity Management
E Karpuzoglu, M Zouali |
Clinical Reviews in Allergy & Immunology | 2009 |
Prolactin alters the mechanisms of B cell tolerance induction
S Saha, J Gonzalez, G Rosenfeld, H Keiser, E Peeva |
Arthritis & Rheumatism | 2009 |
Prolactin, Systemic Lupus Erythematosus, and Autoreactive B Cells: Lessons Learnt from Murine Models
S Saha, A Tieng, KP Pepeljugoski, G Zandamn-Goddard, E Peeva |
Clinical Reviews in Allergy & Immunology | 2009 |
Aging and estrogen: modulation of inflammatory responses after injury
CR Gomez, TP Plackett, EJ Kovacs |
Experimental Gerontology | 2007 |
Diminished prolactin from chlordecone treatment in ovariectomized (NZBxNZW)F(1) mice
F Wang, SM Roberts, EJ Butfiloski, ES Sobel |
International Immunopharmacology | 2007 |
Autoimmune glomerulonephritis with spontaneous formation of splenic germinal centers in mice lacking the estrogen receptor alpha gene
GJ Shim, LL Kis, M Warner, JA Gustafsson |
Proceedings of the National Academy of Sciences | 2004 |
Prolactin modulates the naive B cell repertoire
Elena Peeva, Daniel Michael, James Cleary, Jeffrey Rice, Xian Chen, Betty Diamond |
Journal of Clinical Investigation | 2003 |
Effects of Prolactin on Cloned Human T-Lymphocytes
Z Dogusan, N Martens, P Stinissen, N Hellings, N Demotte, R Hooghe, EL Hooghe-Peters |
Endocrine | 2003 |
Pathogenesis of systemic lupus erythematosus
Mok CC, Lau CS |
Journal of clinical pathology | 2003 |
Estrogen alters thresholds for B cell apoptosis and activation
Christine M. Grimaldi, James Cleary, A. Selma Dagtas, Dariush Moussai, Betty Diamond |
Journal of Clinical Investigation | 2002 |