Abstract

The purpose of this research project is to examine the capacities of lymphopoietic progenitors to generate certain antigen-reactive B cell subsets in adoptive transfer. A novel transplantation model will be employed involving unirradiated immunodeficient xid mice which are unable to mount anti-phosphorylcholine (PC) PFC responses. By using unirradiated hosts, the forced competition between the engrafted donor cells and the intact host cells for the opportunity to develop into the mature state should closely approximate the normal situation in ontogeny; by studying stem cell differentiation under relatively normal, or nondisruptive, conditions, even subtle distinctions between the regeneration abilities of precursors to different antigen-reactive subsets will be accentuated. Thus, the experimental system offers a sensitive means for analyzing the population dynamics of emerging B cell subpopulations. Furthermore, by utilizing the PC system, the ability to partition responses in terms of dominant and nondominant idiotypes will provide an additional level of discrimination. The transplantation of stem cells into precisely and minimally altered environments, and the monitoring of the related, idiotypically well-defined antigen-reactive subsets generated by the engrafted cells will provide information not only on the generation and diversification of B cell lineages, but also with respect to the clonal relationships within functionally delineated B cell compartments. We believe that our experiments will provide new information on normal and abnormal murine lymphopoiesis.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI019589-03
Application #
3128927
Study Section
Immunological Sciences Study Section (IMS)
Project Start
1984-09-01
Project End
1987-08-31
Budget Start
1986-09-01
Budget End
1987-08-31
Support Year
3
Fiscal Year
1986
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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