This new Program Project will unite four established investigators in studies of the development and senescence of the human immune system. The Program Project evolved from the realization by Drs. Kincade, Thompson, and Webb that much very basic information available for the murine immune system is lacking for humans, making it difficult for them to extend their recent exciting findings made with mice to humans. However, new technologies make it difficult for them to extend their recent exciting findings made with mice to humans. However, new technologies and model systems now make it feasible to undertake molecular studies with human lymphocyte precursors and minor subsets of mature cells. Dr. Capra , the fourth investigator, was already, and will continue to be, focused on the human humoral immune response. The four projects are highly integrated and cover many aspects of lymphocyte development. Drs. Thompson and Kincade will study early events in the differentiation of T and B lymphocytes, respectively. Drs. Kincade and Capra will examine the effects of aging on B cell development with Dr. Kincade's efforts focused on early stages and Dr. Capra's on the alter antibody-forming phases. Dr. Webb will study the expression and function of a B cell transcription factor at all stages of forming phases. Dr. Webb will study the expression and function of a B cell transcription factor at all stages of forming phases. Dr. Webb will study the expression and function of a B cell transcription factor at all stages of B cell differentiation with a goal of understanding its role in X-linked a gamma globulinemia.. All four projects involve characterization and/or use of discrete populations of human lymphocytes, making the Flow Cytometry Core with a new MoFlo flow cytometer an integral part of the Program Project. The four investigators will share rare populations of cells as well as molecular techniques for their characterization. The smooth functioning of the Program Project is also assured through an Administrative Core. The combined efforts of the four Project Leaders will yield new insights into the molecular events in human lymphocyte development and abnormalities which occur in immunodeficiencies, autoimmunity, malignancies, and aging.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
1P01AI045864-01
Application #
2898537
Study Section
Special Emphasis Panel (ZAI1-SCO-I (M1))
Program Officer
Quill, Helen R
Project Start
1999-09-30
Project End
2003-08-31
Budget Start
1999-09-30
Budget End
2000-08-31
Support Year
1
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Oklahoma Medical Research Foundation
Department
Type
DUNS #
937727907
City
Oklahoma City
State
OK
Country
United States
Zip Code
73104
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Yokota, Takafumi; Huang, Jiaxue; Tavian, Manuela et al. (2006) Tracing the first waves of lymphopoiesis in mice. Development 133:2041-51
Igarashi, Hideya; Medina, Kay L; Yokota, Takafumi et al. (2005) Early lymphoid progenitors in mouse and man are highly sensitive to glucocorticoids. Int Immunol 17:501-11
Rajaiya, Jaya; Hatfield, Melissa; Nixon, Jamee C et al. (2005) Bruton's tyrosine kinase regulates immunoglobulin promoter activation in association with the transcription factor Bright. Mol Cell Biol 25:2073-84
Chain, J L; Joachims, M L; Hooker, S W et al. (2005) Real-time PCR method for the quantitative analysis of human T-cell receptor gamma and beta gene rearrangements. J Immunol Methods 300:12-23
Yao, Longbiao; Yokota, Takafumi; Xia, Lijun et al. (2005) Bone marrow dysfunction in mice lacking the cytokine receptor gp130 in endothelial cells. Blood 106:4093-101
Nixon, Jamee C; Rajaiya, Jaya B; Ayers, Neil et al. (2004) The transcription factor, Bright, is not expressed in all human B lymphocyte subpopulations. Cell Immunol 228:42-53
Kolar, Grant R; Yokota, Takafumi; Rossi, Maria Isabel D et al. (2004) Human fetal, cord blood, and adult lymphocyte progenitors have similar potential for generating B cells with a diverse immunoglobulin repertoire. Blood 104:2981-7
Kolar, G R; Capra, J D (2004) Immunoglobulin heavy-chain receptor editing is observed in the NOD/SCID model of human B-cell development. Scand J Immunol 60:108-11
Nixon, Jamee C; Rajaiya, Jaya; Webb, Carol F (2004) Mutations in the DNA-binding domain of the transcription factor Bright act as dominant negative proteins and interfere with immunoglobulin transactivation. J Biol Chem 279:52465-72

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