Accession Number : ADA570138


Title :   Determination of the Role of Estrogen Receptors and Estrogen Regulated Genes in B cell Autoreactivity. Addendum


Descriptive Note : Final rept. 1 Jul 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/a570138.pdf


Report Date : Jul 2012


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 estrogeninduced 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 estrogen-nonresponsive (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 , *LUPUS ERYTHEMATOSUS , AUTOIMMUNE DISEASES , AUTOIMMUNIZATION , B LYMPHOCYTES , DEOXYRIBONUCLEIC ACIDS , GENES , GENETICS , RECEPTOR SITES(PHYSIOLOGY) , SENSE ORGANS


Subject Categories : Anatomy and Physiology
      Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE