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

Activation of autoreactive B cells b...

Boston University.

Linked to FindBook

Google Book

Amazon

博客來

Activation of autoreactive B cells by mammalian DNA.

Record Type:	Language materials, printed : Monograph/item
Title/Author:	Activation of autoreactive B cells by mammalian DNA./
Author:	Uccellini, Melissa Boule.
Description:	152 p.
Notes:	Adviser: Ann Marshak-Rothstein.
Contained By:	Dissertation Abstracts International69-03B.
Subject:	Health Sciences, Immunology. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoeng/servlet/advanced?query=3308165
ISBN:	9780549546979

Activation of autoreactive B cells by mammalian DNA.
Uccellini, Melissa Boule.

Activation of autoreactive B cells by mammalian DNA. - 152 p.

Adviser: Ann Marshak-Rothstein.

Thesis (Ph.D.)--Boston University, 2008.

Systemic lupus erythematosus (SLE) and other autoimmune diseases are characterized by the development of autoantibodies directed against a limited subset of nucleic acid-containing autoantigens including DNA, chromatin, and ribonucleoproteins. In addition, defects in the clearance of apoptotic debris have been associated with the development of anti-nuclear antibodies and autoimmune disease. How autoantibodies to DNA develop is problematic, since mammalian DNA is a poor immunogen compared to microbial DNA.

ISBN: 9780549546979Subjects--Topical Terms:

1017716
Health Sciences, Immunology.

Activation of autoreactive B cells by mammalian DNA.
LDR:02958nam 2200289 a 45 001 858197
005 20100712
008 100712s2008 ||||||||||||||||| ||eng d
020 $a 9780549546979
035 $a (UMI)AAI3308165
035 $a AAI3308165
040 $a UMI $c UMI
100 1 $a Uccellini, Melissa Boule. $3 1025231
245 1 0 $a Activation of autoreactive B cells by mammalian DNA.
300 $a 152 p.
500 $a Adviser: Ann Marshak-Rothstein.
500 $a Source: Dissertation Abstracts International, Volume: 69-03, Section: B, page: 1559.
502 $a Thesis (Ph.D.)--Boston University, 2008.
520 $a Systemic lupus erythematosus (SLE) and other autoimmune diseases are characterized by the development of autoantibodies directed against a limited subset of nucleic acid-containing autoantigens including DNA, chromatin, and ribonucleoproteins. In addition, defects in the clearance of apoptotic debris have been associated with the development of anti-nuclear antibodies and autoimmune disease. How autoantibodies to DNA develop is problematic, since mammalian DNA is a poor immunogen compared to microbial DNA.
520 $a Autoreactive B cells are activated by chromatin-containing immune complexes (ICs) through dual engagement of the B cell receptor (BCR) and Toll-like receptor 9 (TLR9), although the nature of the mammalian DNA ligand is unknown. We have examined the contribution of endogenous DNA sequence elements in this process. We find that the presence of CpG dinucleotides is essential for activation of IC and DNA-reactive B cells, and that DNA fragments containing CpG islands can serve as an endogenous source of unmethylated CpG-rich DNA.
520 $a We have also examined the contribution of the BCR to activation of autoreactive B cells. We find that the BCR mediates selective binding and uptake of DNA fragments for delivery to TLR9. Only DNA-reactive B cells are able to proliferate in response to DNA fragments, confirming the critical role of the BCR in delivery of DNA to TLR9. Despite the importance of the BCR in delivery of DNA to TLR9, crosslinking of the BCR by DNA fragments lacking CpG dinucleotides, is unable to induce autoreactive B cell proliferation, indicating that crosslinking alone is insufficient to activate low affinity autoreactive B cells. Engagement of the BCR and TLR9 by CpG-rich DNA, but not non-CpG DNA, results in the activation of extracellular signal-related kinase 1 and 2 (Erk1/2), which may represent a unique signal activated upon coengagement of the two receptors. We also find that certain environmental factors such as the presence of interferon-alpha (IFN-alpha) can modulate BCR signaling leading to enhancement of TLR9 responses to non-CpG DNA.
590 $a School code: 0017.
650 4 $a Health Sciences, Immunology. $3 1017716
690 $a 0982
710 2 $a Boston University. $3 1017454
773 0 $t Dissertation Abstracts International $g 69-03B.
790 $a 0017
790 1 0 $a Marshak-Rothstein, Ann, $e advisor
791 $a Ph.D.
792 $a 2008
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoeng/servlet/advanced?query=3308165