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The role of individual estrogen rece...

Yeshiva University.

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The role of individual estrogen receptors in B cell maturation and tolerance.

Record Type:	Language materials, printed : Monograph/item
Title/Author:	The role of individual estrogen receptors in B cell maturation and tolerance./
Author:	Hill, Latia.
Description:	261 p.
Notes:	Adviser: Betty Diamond.
Contained By:	Dissertation Abstracts International70-02B.
Subject:	Biology, Cell. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoeng/servlet/advanced?query=3348171
ISBN:	9781109037081

The role of individual estrogen receptors in B cell maturation and tolerance.
Hill, Latia.

The role of individual estrogen receptors in B cell maturation and tolerance. - 261 p.

Adviser: Betty Diamond.

Thesis (Ph.D.)--Yeshiva University, 2009.

Systemic Lupus Erythematosus (SLE) is an autoimmune disease characterized by anti-nuclear antibodies. SLE occurs nine times more often in women than men and several lines of evidence suggest a hormonal role. This led us to study hormonal modulation of R4A transgenic mice. R4A is an anti-dsDNA heavy chain transgene. BALB/c mice expressing this transgene normally maintain tolerance. When treated with estradiol (E2), the B cells expressing the transgene are expanded in the spleen and there are increased anti-dsDNA serum titers, and increased frequency of high affinity, DNA-reactive, transgene-expressing B cells in the mature naive splenic B cell subset. We sought to determine which estrogen receptor (ER) was responsible for the changes in B cell repertoire and the anti-DNA titers in R4A transgenic mice. R4A transgenic mice with a targeted deletion of ERalpha or ERbeta were bred and treated with E2 or placebo (P). WT mice, when given E2, display decreased transitional B cells and an expanded marginal zone (MZ) B cell population when compared to P. ERbeta deficient and ERalpha deficient mice are capable of mediating the decrease in transitional B cells and the expansion of the MZ B cells. However, only ERbeta deficient mice displayed increased anti-DNA titers and altered B cell repertoire when compared to P. Since ERalpha is responsible for the break in tolerance, we chose to confirm these observations with WT mice treated with ERalpha specific agonists. We were able to recapitulate our observation in the knockout studies in WT mice given DMSO (vehicle), E2 or the ERalpha agonist propyl pyrazole trisphenol (PPT). PPT-treated mice displayed a decrease in transitional B cells and an expanded the MZ B cell population when compared to vehicle. In addition, mice treated with PPT displayed increased anti-DNA titers as well as an altered B cell repertoire when compared to vehicle. These data show the importance of ERalpha in mediating autoreactivity. These data may lead to future pharmacologic developments, specifically targeting ERalpha in autoimmune diseases such as SLE.

ISBN: 9781109037081Subjects--Topical Terms:

1017686
Biology, Cell.

The role of individual estrogen receptors in B cell maturation and tolerance.
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020 $a 9781109037081
035 $a (UMI)AAI3348171
035 $a AAI3348171
040 $a UMI $c UMI
100 1 $a Hill, Latia. $3 1025346
245 1 4 $a The role of individual estrogen receptors in B cell maturation and tolerance.
300 $a 261 p.
500 $a Adviser: Betty Diamond.
500 $a Source: Dissertation Abstracts International, Volume: 70-02, Section: B, page: 0930.
502 $a Thesis (Ph.D.)--Yeshiva University, 2009.
520 $a Systemic Lupus Erythematosus (SLE) is an autoimmune disease characterized by anti-nuclear antibodies. SLE occurs nine times more often in women than men and several lines of evidence suggest a hormonal role. This led us to study hormonal modulation of R4A transgenic mice. R4A is an anti-dsDNA heavy chain transgene. BALB/c mice expressing this transgene normally maintain tolerance. When treated with estradiol (E2), the B cells expressing the transgene are expanded in the spleen and there are increased anti-dsDNA serum titers, and increased frequency of high affinity, DNA-reactive, transgene-expressing B cells in the mature naive splenic B cell subset. We sought to determine which estrogen receptor (ER) was responsible for the changes in B cell repertoire and the anti-DNA titers in R4A transgenic mice. R4A transgenic mice with a targeted deletion of ERalpha or ERbeta were bred and treated with E2 or placebo (P). WT mice, when given E2, display decreased transitional B cells and an expanded marginal zone (MZ) B cell population when compared to P. ERbeta deficient and ERalpha deficient mice are capable of mediating the decrease in transitional B cells and the expansion of the MZ B cells. However, only ERbeta deficient mice displayed increased anti-DNA titers and altered B cell repertoire when compared to P. Since ERalpha is responsible for the break in tolerance, we chose to confirm these observations with WT mice treated with ERalpha specific agonists. We were able to recapitulate our observation in the knockout studies in WT mice given DMSO (vehicle), E2 or the ERalpha agonist propyl pyrazole trisphenol (PPT). PPT-treated mice displayed a decrease in transitional B cells and an expanded the MZ B cell population when compared to vehicle. In addition, mice treated with PPT displayed increased anti-DNA titers as well as an altered B cell repertoire when compared to vehicle. These data show the importance of ERalpha in mediating autoreactivity. These data may lead to future pharmacologic developments, specifically targeting ERalpha in autoimmune diseases such as SLE.
590 $a School code: 0266.
650 4 $a Biology, Cell. $3 1017686
650 4 $a Health Sciences, Immunology. $3 1017716
690 $a 0379
690 $a 0982
710 2 $a Yeshiva University. $3 1017732
773 0 $t Dissertation Abstracts International $g 70-02B.
790 $a 0266
790 1 0 $a Diamond, Betty, $e advisor
791 $a Ph.D.
792 $a 2009
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoeng/servlet/advanced?query=3348171