B cell differentiation centers on changes in immunoglobulin (Ig) gene expression--the production of Ig with high antigen-binding avidity and heavy chain isotype suitable to elicit various physiologic responses to foreign antigen. In the proposed project, the structural features of Ig gene expression will be analyzed in unique, long-term B lymphocyte cell lines (B-Lyl cells) and antigen-specific subclones. In respone to conven- tional stimuli (anti-IgM and lymphokines), these cells initiate high-rate IgM secretion, production of """"""""mature"""""""" heavy chain isotypes (class switching), and heavy chain class switching. Consequently, the molecular events related to Ig gene expression can be analyzed in these cells as an inducible, ongoing process. Using recombinant DNA techniques, the molecular basis for the changes in Ig gene expression will be determined: sequential DNA rearrangements, and structural and quantitative changes in mRNA species. Screening methods for somatic mutation will also be evaluated. These molecular events may then be used to more precisely characterize the regulatory influence of various T lymphocyte subclasses, macrophages, and their soluble product. B-Lyl cells are also notable for their similarity by surface phenotye to a minor B cell population believed to account for the polyclonal Ig production in genetic models of murine SLE. In the future, comparison of B-Lyl cell lines derived from """"""""normal"""""""" and """"""""lupus"""""""" strains may clarify the mechanism of abnormal Ig production in this disease model.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI022678-02
Application #
3134123
Study Section
Allergy and Immunology Study Section (ALY)
Project Start
1985-09-30
Project End
1988-08-31
Budget Start
1986-09-01
Budget End
1987-08-31
Support Year
2
Fiscal Year
1986
Total Cost
Indirect Cost
Name
University of California Los Angeles
Department
Type
Schools of Medicine
DUNS #
119132785
City
Los Angeles
State
CA
Country
United States
Zip Code
90095