The long term goal of this research is to ascertain the molecular mechanisms by which antigen-dependent stimulation of the surface immunoglobulin receptor leads to the activation, proliferation, and differentiation of B lymphocytes. The goal of the proposed study is to elucidate the in vivo regulation of the jun-B proto-oncogene, with particular emphasis on the molecular mechanism(s) underlying the differential expression of jun-B and c-jun upon sIg receptor crosslinking, and to ascertain the function of the Jun-B protein in relation to B cell activation, proliferation and differentiation. Studies will also assess the nature and function of the related sIg receptor-induced TRE-binding complexes. (A) The molecular composition of the sIg receptor-induced TRE-binding complexes will be assessed by DNA-affinity precipitation analysis and UV photo-crosslinking. (B) The nature of the cis-acting regulatory element(s) that mediate sIg receptor activation of jun-B will be identified by deletion mapping studies of the jun-B promoter and the trans-acting regulatory factor(s) that mediate sIg receptor-induction of jun-B will be identified by electrophoretic mobility shift analysis. (C) Antisense oligodeoxynucleotides will be used to specifically block the in vivo synthesis of Jun-B in order to define the role of Jun-B in the activation, proliferation, and differentiation of B cells. The results of the proposed research will provide a molecular explanation regarding how sIg receptors induce alterations in nuclear gene expression and will define the role of Jun-B and TRE-binding complexes in this capacity and in the growth of """"""""resting"""""""" primary B lymphocytes stimulated through sIg. The results may also provide insight on the origin and nature of dysregulation, autonomous, clonal expansions of B cells, such as those associated with malignant diseases of lymphocytes, and may provide a directive for controlling the progression of such B cell-associated dysregulation.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29AI034586-05
Application #
2003976
Study Section
Immunobiology Study Section (IMB)
Project Start
1993-01-01
Project End
1998-07-31
Budget Start
1997-01-01
Budget End
1998-07-31
Support Year
5
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Boston College
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
045896339
City
Chestnut Hill
State
MA
Country
United States
Zip Code
02467