Pamela L. Witte, PhD
Department of Microbiology and Immunology
Director, Immunology and Aging Program
B.S., Biology/Sociology, 1973. Stephen F. Austin State University, Nacogdoches, Texas.
Ph.D., Cell Biology, 1984. Southwestern Graduate School of Biomedical Science, University of Texas Southwestern Medical Center, Dallas.
B-lymphocytes, stromal cells, hematopoiesis, differentiation, aging
We are interested in the cellular and molecular regulation of B-lymphocyte development. B-cells form and reach an immature, but responsive stage, in the hemopoietic tissues of fetal liver and postnatal bone marrow. Soluble factors (cytokines, growth factors and chemokines) involved in the differentiation and expansion of early B-cells are produced by hemopoietic microenvironmental cells. Through work done in my laboratory, we have identified, isolated and studied bone marrow microenvironmental cells (called stromal cells) that support B-cell development. Additionally, we have found that stromal cells augment the survival of plasma cells.
Currently, we have three major research goals: (1) to determine how the production of B-cells is altered by normal physiologic events, such as aging, and (2) to examine the hypothesis that stromal cells are a key regulator of lymphopoiesis in the marrow, and (3) to identify the mechanisms that allow stromal cells to support the longevity of plasma cells in the bone marrow. Our studies into the age-related deficiency of the immune system, in particular, have revealed new concepts about contact of stromal cells with competent lymphocyte progenitor cells, and production of B cells in aged animals. These studies form the foundation for future experiments in which we will design means to supplement B-lymphocyte production in the marrow in order to enhance peripheral immune function in aged animals. The study of lymphopoiesis and hematopoiesis in culture has yielded many substantive findings, but little of the puzzle has been pieced together in situ. We believe the most compelling insight will come from examining native or freshly isolated bone marrow stromal cells.
Johnson, K.M., K. Owen, and P.L. Witte. Aging and developmental transitions in the B cell lineage. International Immunology 14:1313-1323, 2002..
Parkin, K.G., R.P. Stephan, R.G. Apilado, D.A. Lill-Elghanian, K.P. Lee, B. Saha, and P.L. Witte. Expression of cD28 by bone marrow stromal cells and its involvement in B lymphopoiesis. Journal of Immunology 169:2292-2302, 2002.
Minges Wols, H.A., G.H. Underhill, G.S. Kansas, and P.L. Witte. The role of bone marrow-derived stromal cells in the maintenance of plasma cell longevity. Journal of Immunology 169:4213-4221, 2002.
Pifer, J., R.P. Stephen, D.A. Lill-Elghanian, P.T. Le, and P.L. Witte. Role of stromal cells and their products in protecting young and aged B-lineage precursors from dexamthasone-induced apoptosis. Mechanisms of Ageing and Development, 2002.
Pifer, J., R.P. Stephan, D.A. Lill-Elghanian, and P.L. Witte. Role of stromal cells and their products in protecting B-lineage precursors from dexamethasone-induced apoptosis. Mechanisms of Ageing and Development 124:207-218, 2003.