Abstract
It is clear that estrogen can accelerate and exacerbate disease in some lupus-prone mouse strains. It also appears that estrogen can contribute to disease onset or flare in a subset of patients with lupus. We have previously shown estrogen alters B-cell development to decrease lymphopoiesis and increase the frequency of marginal zone B cells. Furthermore, estrogen diminishes B-cell receptor signaling and allows for the increased survival of high-affinity DNA-reactive B cells. Here, we analyze the contribution of estrogen receptor α or β engagement to the altered B-cell maturation and selection mediated by increased exposure to estrogen. We demonstrate that engagement of either estrogen receptor α or β can alter B-cell maturation, but only engagement of estrogen receptor α is a trigger for autoimmunity. Thus, maturation and selection are regulated differentially by estrogen. These observations have therapeutic implications.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Animals
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B-Cell Activating Factor / genetics
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B-Cell Activating Factor / immunology
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B-Cell Activating Factor / metabolism
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B-Lymphocyte Subsets / drug effects
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B-Lymphocyte Subsets / immunology
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B-Lymphocyte Subsets / metabolism
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B-Lymphocytes / drug effects
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B-Lymphocytes / immunology*
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B-Lymphocytes / metabolism
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Blotting, Western
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Estradiol / pharmacology
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Estrogen Receptor alpha / genetics
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Estrogen Receptor alpha / immunology*
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Estrogen Receptor alpha / metabolism
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Estrogen Receptor beta / genetics
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Estrogen Receptor beta / immunology*
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Estrogen Receptor beta / metabolism
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Estrogens / pharmacology
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Female
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Flow Cytometry
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Gene Expression / drug effects
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Male
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Mice, Knockout
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Ovariectomy
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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Sialic Acid Binding Ig-like Lectin 2 / immunology
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Sialic Acid Binding Ig-like Lectin 2 / metabolism
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Signal Transduction / drug effects
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Signal Transduction / immunology*
Substances
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B-Cell Activating Factor
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Estrogen Receptor alpha
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Estrogen Receptor beta
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Estrogens
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RNA, Messenger
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Sialic Acid Binding Ig-like Lectin 2
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Tnfsf13b protein, mouse
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Estradiol