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| Bone marrow transplantation, B cell development, Germinal center reaction | ||||||
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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 transitional and 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. 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 cell compartment. Experiments are therefore aimed at revealing the sites where ethanol affects B cell maintenance and impairs humoral immunity. |
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| Selected Publications | ||||||
| Click Here for a Complete List of Articles | ||||||
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de Vries, V.C., Wasiuk, A., Bennett, K.A., Benson, M.J., Elgueta, R., Waldschmidt T.J. and Noelle, R.J. Mast Cell Degranulation Breaks Peripheral Tolerance. Am J Transplant Jul 22-2009.
Chitu, V., Ferguson, P.J., de Bruijn, R., Schlueter, A.J., Ochoa, L.A., Waldschmidt T.J., Yeung, Y.G. and Stanley, E.R. Primed innate immunity leads to autoinflammatory disease in PSTPIP2-deficient cmo mice. Blood Jul 16-2009. McGill, J., Meyerholz, D.K., Edsen-Moore, M., Young, B., Coleman, R.A., Schlueter, A.J., Waldschmidt T.J., Cook, R.T. and Legge, K.L. Fetal exposure to ethanol has long-term effects on the severity of influenza virus infections. J Immunol. 182(12):7803-8, 2009. Gurung, P., Young, B.M., Coleman, R.A., Wiechert, S., Turner, L.E., Ray, N.B., Waldschmidt T.J., Legge, K.L. and Cook, R.T. Chronic ethanol induces inhibition of antigen-specific CD8+ but not CD4+ immunodominant T cell responses following Listeria monocytogenes inoculation. J Leukoc Biol. 85(1):34-43, 2009. |
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| Department/Program Affiliations |
| Pathology |
| Biosciences |
| Immunology |
| MSTP |