This proposal is designed to delineate and characterize the regulatory mechanism involved in the control of murine immunoglobulin class expression employing B cell cloning assays that facilitate the class switch and restricted or cloned helper T cell populations. Initially, we will continue to examine the role of the B cell in determining isotype expression by analyzing the extent to which B cells exhibit class commitment. This will be done by reducing problems associated with B cell heterogeneity through the separation of primed and unprimed B cells into defined B cell subsets based on s-Ig (e.g. s-IgA, s-IgE), Lyb surface antigens, and Fc receptors. In addition, we will examine the potential for isotype expression of these defined B cell subsets depending upon the nature of the stimulus by using T-dependent and T-independent forms of the antigen. We will then explore the functional relationship between these defined B cell subsets and helper T cells that are involved in the regulation of isotype expression. The parasite-infected mouse model provides a biological system whereby isotypic regulation by T cells may be maximal since these mice produce abnormally high levels of IgE. We will characterize the helper T cell population from such mice with particular emphasis on helper T cells that may be functionally restricted for the IgE isotype. The most powerful approach for determining the role of T cells in the class switch is the use of clonally derived helper T cells. We intend to clone helper T cells to a variety of carriers including parasite antigens and use these lines in B cell cloning assays with defined B cell subsets. Moreover, employing enrichment procedures we will try to generate isotype-specific T cells from both antigen-primed and parasite-infected mice. We will then define the nature of the target B cells as well as possible recognition elements involved when these functionally-restricted T cells are operative. The proposed studies should substantially contribute to our knowledge of the control mechanisms involved in immunoglobulin class production.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI020313-02
Application #
3129872
Study Section
Immunological Sciences Study Section (IMS)
Project Start
1984-09-01
Project End
1987-08-31
Budget Start
1985-09-01
Budget End
1986-08-31
Support Year
2
Fiscal Year
1985
Total Cost
Indirect Cost
Name
University of Texas Health Science Center San Antonio
Department
Type
Overall Medical
DUNS #
800772162
City
San Antonio
State
TX
Country
United States
Zip Code
78229
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Desai, B B; Abraham, K M; Teale, J M (1990) The isotype potential of B cells present in BALB/c mice chronically infected with Mesocestoides corti. Cell Immunol 130:139-49

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