東華大學圖書館 |

Language: English

Help

回圖書館首頁

手機版館藏查詢

Back

Switch To: Labeled | MARC Mode | ISBD

BAFF-R mutation: A novel contributor...

The University of Wisconsin - Madison.

Linked to FindBook

Google Book

Amazon

博客來

BAFF-R mutation: A novel contributor to systemic autoimmunity.

Record Type:	Language materials, printed : Monograph/item
Title/Author:	BAFF-R mutation: A novel contributor to systemic autoimmunity./
Author:	Mayne, Christopher G.
Description:	168 p.
Notes:	Adviser: Colleen E. Hayes.
Contained By:	Dissertation Abstracts International69-09B.
Subject:	Biology, Genetics. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoeng/servlet/advanced?query=3328042
ISBN:	9780549804598

BAFF-R mutation: A novel contributor to systemic autoimmunity.
Mayne, Christopher G.

BAFF-R mutation: A novel contributor to systemic autoimmunity. - 168 p.

Adviser: Colleen E. Hayes.

Thesis (Ph.D.)--The University of Wisconsin - Madison, 2008.

Systemic lupus erythematosus is an autoimmune disease of unknown etiology that reflects autoantibody-mediated damage due to a failure of B lymphocyte tolerance. Since excessive BAFF expression correlates with human and murine lupus, and BAFF signals B cell survival through BAFF-R, it is believed that excessive BAFF-R signaling can subvert B cell tolerance and facilitate lupus development. A/WySnJ mice carry the Bcmd-1 mutant allele of the Baffr gene. Bcmd-1 causes premature B cell death and profound B cell deficiency. During genetic studies of A/WySnJ mice, we noted that many animals developed weight loss, patchy fur loss, skin lesions, a hunched posture, and occasionally splenomegaly as they aged. Upon further study, we found BAFF-R-mutant A/WySnJ mice developed a lupus-like syndrome.

ISBN: 9780549804598Subjects--Topical Terms:

1017730
Biology, Genetics.

BAFF-R mutation: A novel contributor to systemic autoimmunity.
LDR:03306nam 2200301 a 45 001 858242
005 20100712
008 100712s2008 ||||||||||||||||| ||eng d
020 $a 9780549804598
035 $a (UMI)AAI3328042
035 $a AAI3328042
040 $a UMI $c UMI
100 1 $a Mayne, Christopher G. $3 1025285
245 1 0 $a BAFF-R mutation: A novel contributor to systemic autoimmunity.
300 $a 168 p.
500 $a Adviser: Colleen E. Hayes.
500 $a Source: Dissertation Abstracts International, Volume: 69-09, Section: B, page: 5178.
502 $a Thesis (Ph.D.)--The University of Wisconsin - Madison, 2008.
520 $a Systemic lupus erythematosus is an autoimmune disease of unknown etiology that reflects autoantibody-mediated damage due to a failure of B lymphocyte tolerance. Since excessive BAFF expression correlates with human and murine lupus, and BAFF signals B cell survival through BAFF-R, it is believed that excessive BAFF-R signaling can subvert B cell tolerance and facilitate lupus development. A/WySnJ mice carry the Bcmd-1 mutant allele of the Baffr gene. Bcmd-1 causes premature B cell death and profound B cell deficiency. During genetic studies of A/WySnJ mice, we noted that many animals developed weight loss, patchy fur loss, skin lesions, a hunched posture, and occasionally splenomegaly as they aged. Upon further study, we found BAFF-R-mutant A/WySnJ mice developed a lupus-like syndrome.
520 $a Despite having 90% fewer splenic B cells than normal mice, A/WySnJ mice had an 18-fold increased frequency of splenocytes secreting IgM to dsDNA, and increased amounts of circulating IgM and IgG to dsDNA. A/WySnJ mice also displayed renal pathology characteristic of lupus, including proteinuria and glomerular capillary bed destruction. We genetically linked this autoimmunity to Bcmd-1, since congenic AW.Baffr +/+ mice carrying a wild-type allele developed none of these phenotypes.
520 $a We next sought to ascertain how Bcmd-1 could contribute to a loss in self tolerance. To determine if Bcmd-1 is a complete loss-of-function Baffr allele, we produced B6. Bcmd-1 and AW.Baffr-/- congenic mice, and compared them to B6.Baffr-/- and A/WySnJ mice. The Bcmd-1-expressing mice had more B cells with greater maturity than Baffr-/- mice regardless of genetic background, indicating that Bcmd-1 encodes a partially functional BAFF-R. We also compared B6.Bcmd-1, B6. Baffr-/-, AW.Baffr-/-, and A/WySnJ mice for lupus-like phenotypes to determine whether Bcmd-1 is necessary and sufficient for disease. The Baffr -/- allele did not lead to autoimmunity on either genetic background. In contrast, the Bcmd-1 allele was necessary and sufficient for development of low levels of IgM autoantibodies in B6.Bcmd-1 mice. However, additional unidentified A/WySnJ modifier genes were necessary for development of IgG autoantibodies and renal pathology. We propose that in A/WySnJ mice an excess of BAFF per B cell rescues self-reactive B cells through a partially functional BAFF-R in a B lymphopenic environment.
590 $a School code: 0262.
650 4 $a Biology, Genetics. $3 1017730
650 4 $a Health Sciences, Immunology. $3 1017716
690 $a 0369
690 $a 0982
710 2 $a The University of Wisconsin - Madison. $3 626640
773 0 $t Dissertation Abstracts International $g 69-09B.
790 $a 0262
790 1 0 $a Hayes, Colleen E., $e advisor
791 $a Ph.D.
792 $a 2008
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoeng/servlet/advanced?query=3328042