Differential roles of estrogen receptors α and β in control of B-cell maturation and selection.
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.
Center for Autoimmune and Musculoskeletal Disease, The Feinstein Institute for Medical Research, Manhasset, New York 11030, United States of America.
Latia
L
Hill
Venkatesh
V
Jeganathan
Prameladevi
P
Chinnasamy
Christine
C
Grimaldi
Betty
B
Diamond
D000818:Animals; D053264:B-Cell Activating Factor / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D016175:B-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D015153:Blotting, Western; D004958:Estradiol / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression / Q000187:drug effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010052:Ovariectomy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051918:Sialic Acid Binding Ig-like Lectin 2 / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology*
D053264:B-Cell Activating Factor; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens; D012333:RNA, Messenger; D051918:Sialic Acid Binding Ig-like Lectin 2; C505720:Tnfsf13b protein, mouse; D004958:Estradiol