Mice deficient in antigen receptor rearranging activity due to a disruption of the RAG-2 gene have no B or T cells, but all other components of the immune system (macrophages, NK cells) are intact. When rearranged antigen receptor genes are introduced by breeding into the RAG-2 deficient background, discrete populations of lymphoid cells develop which reflect the expression of the introduced gene. When all necessary components of the B cell antigen receptor are expressed, a developmentally and functionally synchronized population of monoclonal B cells develops in the absence of T cells. This murine model will allow the candidate to undertake the study and detailed characterization of primary cells which are intermediates in this developmental process, and to elucidate the factors involved in peripheral B cell activation and somatic hypermutation of the B cell receptor during the humoral immune response. The research has potentially important implications for the understanding of hematologic and immunodeficiency disease, the genesis of lymphoid malignancies, and biologic therapies such as bone marrow transplantation and gene therapy.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Clinical Investigator Award (CIA) (K08)
Project #
1K08AI001259-01
Application #
2057479
Study Section
Special Emphasis Panel (SRC (60))
Project Start
1994-09-01
Project End
1997-08-31
Budget Start
1994-09-01
Budget End
1995-08-31
Support Year
1
Fiscal Year
1994
Total Cost
Indirect Cost
Name
Children's Hospital Boston
Department
Type
DUNS #
076593722
City
Boston
State
MA
Country
United States
Zip Code
02115