The goal of this study is to identify the functional diversity (D) segments of the human immunoglobulin heavy chain (IgH) gene and to obtain insights into the molecular mechanism of VDJ recombination in this gene. Experiments are proposed herein to study the entire repertoire of human functional D segments by molecular cloning of functionally rearranged IgH sequences and to characterize the genomic organization of the whole repertoire of D segments. An in vivo assay system of DJ and VDJ recombination will be developed and used to elucidate the molecular basis of VDJ recombination. For this purpose, a series of DNA constructs will be made including those with mutated 7mer-9mer signal sequences and spacer sequences and recombination activity will be assayed in the in vivo system. Analyses are also proposed to determine the underlying basis of V segment joining to the DJ complex, by introducing a DNA construct into the assay system.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM039794-02
Application #
3296994
Study Section
Bio-Organic and Natural Products Chemistry Study Section (BNP)
Project Start
1988-09-20
Project End
1991-08-31
Budget Start
1989-09-01
Budget End
1990-08-31
Support Year
2
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Massachusetts Institute of Technology
Department
Type
Schools of Arts and Sciences
DUNS #
City
Cambridge
State
MA
Country
United States
Zip Code
02139