application): The project has the following specific aims. (1) To determine whether the decreased diversity of the B cell repertoire in old mice results from the impaired development of a diverse repertoire in the central (bone marrow) and/or peripheral lymphoid (spleen and lymph nodes) tissues. They will use a novel PCR-based method to measure the heterogeneity of Ig CDR3 sizes to assay the diversity of the B cell repertoire and the appearance of clonal B cell populations in 3, 12, and 18 month old mice. They will also analyze the frequency of somatic mutations in an anti-H-2 antibody expressed as a transgene in RAG-1 deficient mice given syngeneic t cells from 3,12, and 18 month old mice. Finally, they shall determine the immunological consequences of monoclonal B cell expansions observed in old mice on the immune response. (2) To develop strategies to overcome the constraints in B cell development and somatic mutation in old mice. They will test the capacity of an immunoglobulin transgene, and inducible RAG genes to normalize B cell development in old mice. They will also determine whether T cells from young mice or TCP-17 can overcome the reported impaired capacity of T cells from old mice to support somatic mutation of transgene in a RAG-deficient environment. Finally, they will test the capacity of TCP-17 to increase RAG gene expression. VDJ rearrangement as well as the decreased rate of generating peripheral B cells in old mice.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Program Projects (P01)
Project #
5P01AG014669-03
Application #
6344597
Study Section
Project Start
2000-08-15
Project End
2003-06-30
Budget Start
1998-10-01
Budget End
1999-09-30
Support Year
3
Fiscal Year
2000
Total Cost
$219,703
Indirect Cost
Name
Weill Medical College of Cornell University
Department
Type
DUNS #
201373169
City
New York
State
NY
Country
United States
Zip Code
10065
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LeMaoult, J; Messaoudi, I; Manavalan, J S et al. (2000) Age-related dysregulation in CD8 T cell homeostasis: kinetics of a diversity loss. J Immunol 165:2367-73

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