The hypothesis that will be tested in this proposal is that proteins that regulate IgH enhancer activity also regulate early B cell differentiation.
The specific aims are: 1. To correlate a decrease in Id transcription, and increases in E2-5 and Oct-2 activity, with the onset of IgH enhancer activity in differentiating B cells. (Oct-2 is a B-- cell-specific transcription factor that activates both the IgH enhancer and VH-region promoters.) 2. To block the initiation of B cell differentiation by overexpressing Id, antisense E2-5, and antisense Oct-2, individually and in combinations, thereby testing whether a decrease in Id, or increases in E2-5 or Oct-2, are necessary for the initiation of B cell differentiation. 3. To induce B cell differentiation by overexpressing E2-5, Oct-2, and antisense Id, individually and in combinations, thereby testing whether a decrease in Id, or increases in E2-5 or Oct-2, are sufficient for the initiation of B cell differentiation. Two in vitro model systems for B cell differentiation will be used: coculture of LyD9 cells with bone marrow stromal cells and Whitlock-Witte bone marrow culture. Electroporation and retroviral transfer will be used to introduce genes into cells.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08HL002871-03
Application #
2210708
Study Section
Special Emphasis Panel (ZHL1-CCT-M (02))
Project Start
1993-03-01
Project End
1996-02-29
Budget Start
1995-03-01
Budget End
1996-02-29
Support Year
3
Fiscal Year
1995
Total Cost
Indirect Cost
Name
University of Pennsylvania
Department
Pathology
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104