Abstract

The long term goal of the proposed research is to determine how T cells and lymphokines from T cells regulate the growth of B cells. Studies are planned in two major areas: (1) Function of B cell growth factors (BCGFs), (2) Role of T cells in activation of BCGF-responsive B cells. (1) Several aspects of the function of BCGFs will be addressed, including: (a) preparation and biochemical characterization of two distinct BCGFs (designated BCGFI [BSFpl] and BCGFII) for use in our own studies and in collaborative studies; (b) effects of these BCGFs on potential subpopulations of B cells defined by function, size, density, and cell surface markers; (c) effects on BCGFs on B cell growth cycle on kinetics of growth and on B cell response to other lymphokines; (d) attempts to develop in vitro clones of B cells maintained on, and responsive to, BCGFs. (2) Helper T cells will be compared to other agents in the activation of B cells for their response to BCGFs. (a) T cell hybridomas which activate B cells will be developed and compared with bulk populations of T cells for their ability to activate B cells; (b) B cell activation will be monitored by increase in B cell size, by exit of B cells from the resting G0 state, and by acquisition of responsiveness to BCGFI and BCGFII; (c) Anti-Ig and B cell mitogens lipopolysaccharide and dextran sulfate will be compared with T cells in these steps; (d) the role of lymphokines including IL1 and factors produced by the activating T cell hybridomas in B cell activation will be determined. In these studies, standard biochemical and molecular techniques will be used in combination with the in vitro culture of separated populations of normal and malignant B cells. The results of these studies will help us to understand the stages of the B cell life cycle and the regulation of those phases important in normal and malignant growth. These findings can help develop model systems to study further the mechanisms of oncogenesis which result in unregulated cell growth.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI022125-03
Application #
3132850
Study Section
Experimental Immunology Study Section (EI)
Project Start
1985-09-30
Project End
1990-08-31
Budget Start
1987-09-01
Budget End
1988-08-31
Support Year
3
Fiscal Year
1987
Total Cost
Indirect Cost

  Institution

Name
University of California San Diego
Department
Type
Schools of Medicine
DUNS #
077758407
City
La Jolla
State
CA
Country
United States
Zip Code
92093

  Publications

Kamperschroer, Cris; Roberts, Deborah M; Zhang, Yongqing et al. (2008) SAP enables T cells to help B cells by a mechanism distinct from Th cell programming or CD40 ligand regulation. J Immunol 181:3994-4003
Kamperschroer, Cris; Dibble, John P; Meents, Dana L et al. (2006) SAP is required for Th cell function and for immunity to influenza. J Immunol 177:5317-27
Harris, D P; Haynes, L; Sayles, P C et al. (2000) Reciprocal regulation of polarized cytokine production by effector B and T cells. Nat Immunol 1:475-82
Rogers, P R; Dubey, C; Swain, S L (2000) Qualitative changes accompany memory T cell generation: faster, more effective responses at lower doses of antigen. J Immunol 164:2338-46
Swain, S L (2000) CD4 T-cell memory can persist in the absence of class II. Philos Trans R Soc Lond B Biol Sci 355:407-11
Carter, L L; Swain, S L (1998) From naive to memory. Development and regulation of CD4+ T cell responses. Immunol Res 18:1-13
Carter, L L; Zhang, X; Dubey, C et al. (1998) Regulation of T cell subsets from naive to memory. J Immunother 21:181-7
Dubey, C; Croft, M; Swain, S L (1996) Naive and effector CD4 T cells differ in their requirements for T cell receptor versus costimulatory signals. J Immunol 157:3280-9
Croft, M; Swain, S L (1995) Recently activated naive CD4 T cells can help resting B cells, and can produce sufficient autocrine IL-4 to drive differentiation to secretion of T helper 2-type cytokines. J Immunol 154:4269-82
Dubey, C; Croft, M; Swain, S L (1995) Costimulatory requirements of naive CD4+ T cells. ICAM-1 or B7-1 can costimulate naive CD4 T cell activation but both are required for optimum response. J Immunol 155:45-57

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