The immune response results from the interactions of lymphocytes of many specificities and functions. One of these, the helper T cell, is required for the optimal expression of the functions of other subsets of T cells as well as B lymphocytes. The experiments are designed to further our understanding of helper T-cell function and the mechanisms that control their interactions with B lymphocytes. First, we are evaluating the role of interleukin-2 in the responses of B lymphocytes. We have identified a novel Thy-1+ cell that arises in cultures containing interleukin-2, whose function may be to induce resting B cells to enter cell cycle. We are continuing studies directed at understanding this population. Second, we are evaluating the function of surface immunoglobulin and class II molecules in the triggering of B lymphocytes. Using a B-cell lymphoma that expressed I-A snd I-E molecules but utilizes only I-E molecules as triggering receptors, we are evaluating the relative mobilities of these molecules in the membrane, their numbers, and the dynamics of these molecules in the membrane of unactivated and activated cells. Third, we are investigating the selective use of the I-E molecule as a triggering receptor and its relationship with the expression of certain immunoglobulin V regions during the immune response (i.e., immune response gene control of B-cell idiotypes). Together, these studies will provide information necessary to understand the regulation of interactions of functionally distinct subpopulations of lymphocytes, the basis of specificity in the immune response, and the selection of the B-lymphocyte repertoire. The results of these experiments will also provide insights into the nature of aberrant lymphocyte responses and growth. (LB)

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA036642-08
Application #
3174243
Study Section
Immunobiology Study Section (IMB)
Project Start
1987-07-01
Project End
1989-06-30
Budget Start
1988-07-01
Budget End
1989-06-30
Support Year
8
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Duke University
Department
Type
Schools of Medicine
DUNS #
071723621
City
Durham
State
NC
Country
United States
Zip Code
27705
Doerre, Stefan; Mesires, Kristin Perkins; Daley, Kylle M et al. (2005) Reductions in I kappa B epsilon and changes in NF-kappa B activity during B lymphocyte differentiation. J Immunol 174:983-91
Flemming, Jennifer A; Perkins, Kristin H; Luus, Lia et al. (2004) Disruption of membrane cholesterol stimulates MyD88-dependent NF-kappaB activation in immature B cells. Cell Immunol 229:68-77
Reddy, P S; Corley, R B (1999) The contribution of ER quality control to the biologic functions of secretory IgM. Immunol Today 20:582-8
Doerre, S; Corley, R B (1999) Constitutive nuclear translocation of NF-kappa B in B cells in the absence of I kappa B degradation. J Immunol 163:269-77
Reddy, P S; Corley, R B (1998) Assembly, sorting, and exit of oligomeric proteins from the endoplasmic reticulum. Bioessays 20:546-54
Brewer, J W; Randall, T D; Parkhouse, R M et al. (1994) IgM hexamers? Immunol Today 15:165-8
Randall, T D; Lund, F E; Brewer, J W et al. (1993) Interleukin-5 (IL-5) and IL-6 define two molecularly distinct pathways of B-cell differentiation. Mol Cell Biol 13:3929-36
Lund, F E; Randall, T D; Woodland, D L et al. (1993) MHC class II limits the functional expression of endogenous superantigens in B cells. J Immunol 150:78-86
Corley, R B; Lund, F E; Randall, T D et al. (1992) Mouse mammary tumor proviral gene expression in cells of the B lineage. Semin Immunol 4:287-96
Lund, F E; Corley, R B (1991) Regulated expression of mouse mammary tumor proviral genes in cells of the B lineage. J Exp Med 174:1439-50

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