It has long been disputed whether sex hormones play a role in immune regulation and specifically in systemic lupus erythematosus. We have demonstrated that estradiol can alter the threshold for negative selection of naive autoreactive B cells. Estradiol, at 75 l00pg/ml will break tolerance for anti-DNA marginal zone B cells in BALB/c mice, but not in C57Bl/6 mice. We have further demonstrated that the survival of autoreactive B cell is distinct from activation of these cells. We now propose to understand what genes and pathways are involved in estrogen-mediated B cell survival and B cell activation. We will ask how estrogen leads to an increase specifically cells in the marginal zone B cell subset. Finally, we will investigate the differences in B cell responsiveness to estrogen in BALB/c and C57Bl/6 mice to understand what underlies an estrogen mediated breakdown in humoral self- tolerance.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
1R01AI051767-01
Application #
6484820
Study Section
Special Emphasis Panel (ZAI1-NN-I (J2))
Program Officer
Esch, Thomas R
Project Start
2002-07-01
Project End
2006-06-30
Budget Start
2002-07-01
Budget End
2003-06-30
Support Year
1
Fiscal Year
2002
Total Cost
$417,500
Indirect Cost
Name
Albert Einstein College of Medicine
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
009095365
City
Bronx
State
NY
Country
United States
Zip Code
10461
Jeganathan, Venkatesh; Peeva, Elena; Diamond, Betty (2014) Hormonal milieu at time of B cell activation controls duration of autoantibody response. J Autoimmun 53:46-54