Research Interest: Germinal Center biology; Influenza; Tregs
The Waldschmidt lab is very interested in germinal center (GC) biology. The GC reaction in secondary lymphoid tissues is an important site of T cell-dependent humoral responses to infection. Antigen-specific B cells enter the GC and undergo intense expansion, somatic hypermutation, affinity maturation, and isotype switching. Consequently, GC responses generate long-lived memory B cells and antibody-secreting plasma cells, both of a selected high affinity. Previous work in our lab has shown the GC reaction to exhibit steady state characteristics in the spleen. This is best exemplified by a steady ratio of non-switched (IgM+) to switched (IgM-) GC B cells over the course of the GC response. The steady state nature of the GC reaction mandates strict regulation, and our laboratory has implicated T regulatory (T reg) cells in this process. Previous work in the lab has only focused on GC responses to experimental antigens (SRBC, NP-KLH, and Phycoerythrin) under Th2 conditions.
One of my current projects in the lab is to better understand the basic humoral immune response to influenza virus by infecting mice with H1N1 strains of flu, which is not only a natural pathogen, but activates B cells under Th1 conditions. Preliminary experiments injecting flu virion i.p. suggest that splenic GCs exhibit steady-state characteristics and that Tregs play a role in maintaining GC homeostasis after such a challenge - results that are similar to those obtained from experiments using experimental Th2-polarizing challenges. It is also of interest to study the GC response to a pulmonary infection with influenza A virus and preliminary challenges intranasally reveal not only GCs in the lung-draining lymph nodes and lung tissue itself (presumed to be iBALT), but also robust and sustained GCs in the spleen. Tregs seem to be playing a role in GC homeostasis in these experiments as well. Other current projects seek to understand not only the complete humoral response to infection (serum antibody, antibody-forming cells, T cell help, etc,) but also the spread of virus/viral products from the lung following pulmonary infection.
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