Accession Number:

ADA549046

Title:

Determination of the Role of Estrogen Receptors and Estrogen Regulated Genes in B Cell Autoreactivity

Descriptive Note:

Annual rept. 1 Jul 2010-30 Jun 2011

Corporate Author:

FEINSTEIN INST FOR MEDICAL RESEARCH MANHASSET NY

Personal Author(s):

Report Date:

2011-07-01

Pagination or Media Count:

32.0

Abstract:

Systemic lupus erythematosus is an autoimmune disease that occurs preferentially in women. We have developed a murine model in which BALBc non-spontaneously autoimmune mice harbor a transgene encoding the heavy chain of an anti-DNA antibody. Using this model, we have shown that B cell expression of the estrogen receptor ER mediates an estrogen-induced loss of B cell tolerance. This occurs through a reduced B cell receptor BCR signal strength in transitional B cells and the presence of DNA is required to mediate positive selection of the autoreactive B cells. Moreover, estrogen-induced autoimmunity depends on the genetic background. Exploiting the availability of an estrogen-responsive BALBc strain and an estrogennonresponsive C57Bl6 strain, we have found that estrogen upregulates p202b, an anti-apoptotic factor, and itpkb, a molecular that limits the release of calcium stores, in BALBc mice protecting autoreactive B cells from BCR-triggered apoptosis and impairing negative selection during B cell development.

Subject Categories:

  • Anatomy and Physiology
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE