The long range goal of this work is to understand the function, development, and differentiation of Ly-1 B cells. These B cells constitute a small population first identified by their expression of the pan T cell marker CD5. They differ in many respects from the majority of B cells that do not express CD5 (conventional B cells), disproportionate representation among B cell neoplasias. We have previously identified a bias in immunoglobulin variable (V) gene use in peritoneal Ly-1 B cells due to antigen selection. 5-15% of Ly-1 B cells are specific for the hapten phosphatidyl choline (PtC) and use either of two heavy (H) and light (L) chain V gene combinations. No conventional B cells with this specificity are detected. We propose to extend this work by examining the use of other V genes for evidence of positive and negative selection. This will be done by comparing variable H gene expression by Ly-1 and conventional B cells using cDNA libraries derived from cells of each population, and by examining V gene use in Ly-1 B cell hybridomas. We also propose to examine the basis for the absence of detectable numbers of PtC specific conventional B cells by creating a transgenic mouse model in which the rearranged H and L chain genes for an anti-PtC antibody are introduced into the germline. The fate of conventional PtC specific B cells will be determine by flow cytometry. In addition, we will assess the expressed V gene repertoire of Ly-1 B cells from mice homozygous for the viable motheaten (me) mutation. These mice suffer from a severe autoimmune and immune deficiency disease derive from Ly-1 B cells, since all IgM producing B cells in (me) mice are Ly-1. We propose to determine whether the production of pathological autoantibodies is the result of selection by antigen as is the case in mice of other autoimmune strains, or polyclonal stimulation.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI029576-03
Application #
3144444
Study Section
Allergy and Immunology Study Section (ALY)
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
University of North Carolina Chapel Hill
Department
Type
Schools of Medicine
DUNS #
078861598
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599