Pamela L. Witte, Ph.D.
Professor

Ph.D., University of Texas

Cellular Immunologist

The cellular and molecular regulation of B-lymphocyte development

Although as many as one-fourth of the cells in bone marrow are committed to become B-lineage cells, the mechanisms that orchestrate development of B cells are difficult to determine because seven other blood-cell lineages also differentiate from the same common progenitor cell. Recent experiments show that cytokines interleukin-7 and stem cell factor are involved in the differentiation and expansion of early B cells. These cytokines are produced by hemopoietic microenvironmental cells called stromal cells, which are pivotal to lympho/hemopoietic regulation. B-cell production is sensitive to a variety of stimuli, such as chemical and irradiation treatments and infectious agents, and normal processes such as aging appear selectively perturb marrow lymphopoiesis.

Currently, our major goals are (1) to define the nature and heterogeneity of the bone marrow stromal cells in vivo; (2) to understand how they respond to marrow-ablative treatments as well as to normal physiologic events such as aging, and (3) to delineate events that regulate the function of marrow reticular stromal cells. To investigate these issues, we have devised new methods to isolate stromal cells and have generated a panel of monoclonal antibodies that define the marrow stromal cells and functional subsets in normal tissues. We are using molecular techniques to explore the types of cytokines produced by individual stromal cells.

Although we have made progress in tissue culture models of B-cell development, very little of the puzzle has been pieced together in situ. Our present and future studies will attempt to resolve the normal microenvironment that guides B-cell formation.

Selected Publications

Minges Wols, H. A.,  Ippolito, J. A., Yu, Z., Palmer, J. L., White, F. A., Le, P. T., Witte, P. L. (2007). The effects of microenvironment and internal programming on plasma cell survival. Int Immunol. Jul;19(7):837-46.

Faunce, DE. J.L. Palmer, K.K. Paskowicz, P.L. Witte, and E.J. Kovacs. (2005). CD1d-restricted NKT cells contribute to the age-associated decline of T cell immunity. J. Immunol. 175:3102-3109.

Pifer, J., Stephan, R.P., D.A. Lill-Elghanian, and P.L. Witte. (2003). Role of Stromal Cells and their Products in Protecting B-lineage Precursors from Dexamethasone-induced Apoptosis. Mechanisms of Ageing and Development 124:207-2 18.

Minges Wols, H.A., G.H. Underhill, G.S. Kansas, and P.L. Witte. (2002). The Role of Stromal Cells in the Maintenance of Plasma Cell Survival. J. Immunol. 169:4213-4221.

Johnson, K.M., K. Owen, and P.L. Witte. (2002). Aging and Developmental Transitions in the B-cell Lineage. International Immunology 14:1313-1323.

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