The mechanisms underlying the negative regulation of self-reactive B cells that arise during antigen-driven B cell responses remain obscure. The project described in this fellowship application centers on understanding the role of the cytokine BAFF in the regulation of DNA-reactive B cells that enter the germinal center B cell response. Through the use of unique transgenic mouse lines, the influence of BAFF on the fate of self-reactive B cells will be determined.
The specific aims are: 1) determine whether BAFF expression by follicular helper T cells alters counter-selection of self-reactive germinal center B cells;and 2) determine whether changes in germinal center B cell TACI receptor expression disturb the counter-selection of self-reactive germinal center B cells. These studies will provide fundamental information on the regulation of self-reactive B cells, which are the source of pathogenic antibodies in a variety of autoimmune disorders including Lupus, and will therefore fulfill the mission of the Transfusion Medicine and Cellular Therapeutics program of the NIHLB.

Public Health Relevance

The proposed studies will test whether exposure of activated DNA-reactive B cells to BAFF, a soluble protein produced by a variety of immune system cells, increases the likelihood that such cells will produce pathogenic antibodies. This work will increase understanding of the mechanisms underlying lupus and related autoimmune disorders.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Individual Predoctoral NRSA for M.D./Ph.D. Fellowships (ADAMHA) (F30)
Project #
5F30HL103157-02
Application #
8332944
Study Section
Special Emphasis Panel (ZRG1-F07-C (20))
Program Officer
Chang, Henry
Project Start
2011-09-01
Project End
2013-05-31
Budget Start
2012-09-01
Budget End
2013-05-31
Support Year
2
Fiscal Year
2012
Total Cost
$41,664
Indirect Cost
Name
Thomas Jefferson University
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
053284659
City
Philadelphia
State
PA
Country
United States
Zip Code
19107