Immunoglobulin molecules (Ig) consist of heavy and light chains and are expressed in B-cells to diversity of antigens. Igs acquire their antigen recognition properties in a process of DNA deletion called VDJ recombination. Unsuccessful expression of the recombined Ig leads to failure of B-cell maturation, numerous infections and premature death of the affected individual. Abelson cell lines have the phenotype of a pre-B- cell and have been used to study how Ig expression affects B-cell maturation. The accessibility hypothesis proposes that regulated Ig expression in B-cells is governed in part by the transcriptional and VDJ recombinase activities to target the Ig locus. Recent experiments suggest that selective chromatin reorganization of the Ig locus may play a role in controlling accessibility to transcriptional and recombinase activities in B- cell-specific manner. The experiments proposed in this fellowship exploit inducible light chain (kappa) gene reorganization in Abelson cell lines to develop a highly purified in vitro system that faithfully mimics VDJ recombination signaled Ig locus remodeling. This system will investigate a proposed activity endogenously present in Abelson cells that either specifically recognizes and directly remodels or specifically recognizes and recruits a """"""""general remodeling machinery"""""""" to the kappa locus for chromatin reorganization upon induction of VDJ rearrangement.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32AI010523-01
Application #
6137099
Study Section
Special Emphasis Panel (ZRG1-IMB (01))
Program Officer
Prograis, Lawrence J
Project Start
2001-01-31
Project End
Budget Start
2000-07-01
Budget End
2001-06-30
Support Year
1
Fiscal Year
2000
Total Cost
$37,516
Indirect Cost
Name
Massachusetts Institute of Technology
Department
Type
Organized Research Units
DUNS #
City
Cambridge
State
MA
Country
United States
Zip Code
02139
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