Determination of the Role of Estrogen Receptors and Estrogen Regulated Genes in B Cell Autoreactivity
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.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2011
- Accession Number
- ADA549046
Entities
People
- Betty Diamond
Organizations
- The Feinstein Institute for Medical Research