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) : Diamond, Betty


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a549046.pdf


Report Date : Jul 2011


Pagination or Media Count : 32


Abstract : Systemic lupus erythematosus is an autoimmune disease that occurs preferentially in women. We have developed a murine model in which BALB/c 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 (BALB/c) strain and an estrogennonresponsive (C57Bl/6) strain, we have found that estrogen upregulates p202b, an anti-apoptotic factor, and itpkb, a molecular that limits the release of calcium stores, in BALB/c mice protecting autoreactive B cells from BCR-triggered apoptosis and impairing negative selection during B cell development.


Descriptors :   *ESTROGENS , AUTOIMMUNE DISEASES , B LYMPHOCYTES , DEOXYRIBONUCLEIC ACIDS , GENES , GENETICS , LUPUS ERYTHEMATOSUS , RECEPTOR SITES(PHYSIOLOGY) , SENSE ORGANS , WOMEN


Subject Categories : Anatomy and Physiology
      Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE