Abstract

It is not known how the immune system develops during ontogeny to become a connected network of interacting T and B cells. The long-term goal of this on-going research project is to solve this problem using the T15/PC murine system as a model. Our working hypothesis is that there exist finite resources allocated to B cell differentiation during ontogeny. As a consequence, B cell precursors compete with each and some become winners (dominant idiotypes). T15+ B cell clones have an ontogenetic advantage and compete successfully to reach a developmental stage where IghC-linked network selection occurs to preserve dominant expression of this idiotype. This proposal deals with experiments designed to reconstruct the cellular interactions that bring about T15 dominance. I propose a series of in vivo experiments to analyze the role of antigen, internal images of PC, helper T and B cell subsets in the regulation of T15 expression. Our research addresses important and unresolved issues in immunoregulation: idiotype vs non-idiotype-specific effects, the development of the lymphocyte network and the interdependence of T and B cell repertoires.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
2R01AI019589-04A1
Application #
3128925
Study Section
Immunobiology Study Section (IMB)
Project Start
1984-09-01
Project End
1991-06-30
Budget Start
1988-07-01
Budget End
1989-06-30
Support Year
4
Fiscal Year
1988
Total Cost
Indirect Cost

  Institution

Name
University of Chicago
Department
Type
Schools of Medicine
DUNS #
225410919
City
Chicago
State
IL
Country
United States
Zip Code
60637

  Publications

Gottschalk, A R; Boise, L H; Thompson, C B et al. (1994) Identification of immunosuppressant-induced apoptosis in a murine B-cell line and its prevention by bcl-x but not bcl-2. Proc Natl Acad Sci U S A 91:7350-4
Gottschalk, A R; Joseph, L J; Quintans, J (1994) Fc gamma RII cross-linking inhibits anti-Ig-induced erg-1 and erg-2 expression in BCL1. J Immunol 152:2115-22
Gottschalk, A R; McShan, C L; Merino, R et al. (1994) Physiological cell death in B lymphocytes: I. Differential susceptibility of WEHI-231 sublines to anti-Ig induced physiological cell death and lack of correlation with bcl-2 expression. Int Immunol 6:121-30
Gottschalk, A R; Joseph, L J; Quintans, J (1993) Differential induction of Egr-1 expression in WEHI-231 sublines does not correlate with apoptosis. Eur J Immunol 23:2011-5
Martino, G; Anastasi, J; Feng, J et al. (1993) The fate of human peripheral blood lymphocytes after transplantation into SCID mice. Eur J Immunol 23:1023-8
Mayforth, R D; Quintans, J (1990) Designer and catalytic antibodies. N Engl J Med 323:173-8
Quintans, J (1989) Cellular competition and the promotion of T15 to idiotypic dominance. Immunol Rev 110:119-34
Quintans, J; Yokoyama, A; Evavold, B et al. (1989) Direct activation of murine resting T cells by con A or anti-CD3 Ig. J Mol Cell Immunol 4:225-35;discussion 235-7
Latta, S L; Sosman, J A; Quintans, J (1989) The role of autoreactive T-cell lines in the restoration of the immune response to sheep red blood cells in C57Bl/6-lpr/lpr mice. J Autoimmun 2:15-24
Quintans, J; Wemhoff, G A (1988) B-cell transplants to immunodeficient xid neonates do not imprint their helper T cells. J Mol Cell Immunol 4:97-103

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