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The research in my laboratory is centered on the biology of B lymphocytes. We are interested in many aspects of this population including their development, subset distribution, function, and differentiation in germinal centers. We are further analyzing their reconstitution and function after bone marrow transplantation and their abnormal behavior in disease states. The following projects are ongoing in the laboratory: Development and function of B cell subsets. Our laboratory has a long-standing interest in the diversity of subsets within the B cell lineage. In addition to follicular B cells, the periphery contains B1 B cells, marginal zone B cells and transitional B cells. We are actively exploring the development of these subsets as well as their individual roles in the humoral immune response. Particular interest is focused on the derivation and function of marginal zone B cells. Regulation of the germinal center response in normal and autoimmune mice. Upon T cell-dependent activation of B cells, a series of complex events unfold leading to the generation of germinal centers. These are key sites where isotype switching, somatic hypermutation, affinity maturation and memory cell formation occur. Importantly, we have found that germinal centers are dysregulated in mouse models of lupus. Studies in our laboratory are therefore focused on the cellular and molecular signals that regulate germinal center formation and maintenance, and role of T regulatory cells in this process. Reconstitution and function of B cells after bone marrow transplantation. This project is attempting to understand the lesions that exist in the B cell compartment after transplantation of semi-matched stem cells. Experiments are exploring both in utero and post-natal transplantation models. Effect if ethanol on B cell function: Finally, we have initiated studies to understand the basis of B cell loss and dysfunction in long-term alcoholics. It is well established that chronic alcoholism leads to lesions in both innate and adaptive immunity, with marked effects in the B cells compartment. Experiments are therefore aimed at revealing the sites where ethanol affects B cell maintenance and impairs humoral immunity. Erickson LD, Foy TM, and Waldschmidt TJ. Murine B1 B cells require IL-5 for optimal T cell-dependent activation. J. Immunol. 166:1531, 2001. Waldschmidt TJ, Panoskaltsis-Mortari A, McElmurry RT, Tygrett LT, Taylor PA, and Blazar BR. Abnormal T cell-dependent B cell responses in SCID mice receiving allogeneic bone marrow in utero. Blood 100:4557. 2002. Wolniak KL, Shinall SM, and Waldschmidt TJ. The primary germinal center response. Crit Rev Immunol. 24:39, 2004. Cozine CL, Wolniak KL, Waldschmidt TJ. The primary germinal center response in mice. Curr Opin Immunol. 17:298, 2005. Elzey BD, Grant JF, Sinn HW, Nieswandt B, Waldschmidt TJ, and Ratliff TL. Cooperation between platelet-derived CD154 and CD4+ T cells for optimal early germinal center formation. J. Leuk. Biol. 78:80, 2005. Wolniak KL, Noelle RJ, and Waldschmidt TJ. Flow cytometric characterization of B220+ and B220- antigen-binding splenic subsets after primary NP challenge. Submitted, 2005. |
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