Control of immune function is achieved not only by regulation of soluble products produced by lymphoid and monocytic cells, but also by the specific antigen receptor molecules, major histocompatibility complex molecules, and """"""""accessory"""""""" cell surface molecules that determine the specificity and strength of cell-cell interactions and, in some cases, transduce biochemical signals to the cells' interior. We propose that a failure in immunoregulation, resulting form impaired T-B cell cooperation, contributes to the emergence of the B cell hyperactivity characteristic of autoimmune disease. The present application describes experiments designed to pursue our ongoing investigation of the role of activated B cells in T-B cell interactions, in normal human subjects in those with autoimmune disease.
Our specific aims are to study: 1 Mechanism of Th cell-mediated B cell activation. a) The molecular basis of Th cell-mediated resting B cell activation will be characterized with regard to the roles of interleukin 4 and B cell surface molecules; b) the Th cell subpopulation responsible for delivery of direct T cell help to B cells will be identified; c) the functional properties of the B cell population bearing the CD23 cell surface activation antigen will be characterized. 2. The role of impaired t-B cell interaction in autoimmunity. a) The hypothesis that augmented T cell help, or an increased B cell response to T cell help, contributes to the B cell hyperactivity characteristic of rheumatoid arthritis will be investigated; and b) the role of Th cell-B cell interactions in the augmented polyclonal antibody response and secretion of rheumatoid factor specificities found in rheumatoid arthritis will be studied.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI028367-03
Application #
3142850
Study Section
Immunological Sciences Study Section (IMS)
Project Start
1990-04-01
Project End
1995-03-31
Budget Start
1992-04-01
Budget End
1993-03-31
Support Year
3
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Hospital for Special Surgery
Department
Type
DUNS #
City
New York
State
NY
Country
United States
Zip Code
10021