SVM: Pathology, Microbiology & Immunology
Center for Comparative Medicine
University of California, Davis
Research Interest: The Baumgarth Lab investigates the basic immunological mechanisms that regulate and control immunity to pathogens. They aim to reveal the signals that drive a protective B cell response and to determine how these responses might be derailed by certain pathogens. Two mouse models of infection are being studied: influenza virus and Borrelia burgdorferi, the Lyme Disease agent. They are interested also in understanding the development and the role and function of a small innate-like B cell subset, termed B-1 cells and the natural IgM this subset is producing.
The lab primarily uses mouse-models to study the regulatory processes controlling successful and unsuccessful immune responses. Numerous genetically engineered mice are being used to dissect specific aspects of the immune response. Much of the work relies on in vivo and ex vivo analyses tools such as multiparameter flow cytometry for functional and phenotypic studies, histology and immunohistochemistry, ELISA, ELISPOT, laser-dissection microscopy, microarray/RNAseq and qRT-PCR analysis and other state-of-the-art cellular and molecular immunological assays.
Studies in the Baumgarth lab are conducted in collaboration with many researchers, including Drs. Barboza-Gardner (UC Davis, Dept Chemistry), Kent Lloyd (UC Davis Mouse Biology Program), Scott Simon (UC Davis, Biomedical Engineering), Frances Lund, Troy Randall and Allan Zajac (University of Alabama, Birmingham) and Eun-Frances Lee and Inaki Sanz (Emory University). Dr. Baumgarth also works with Northrup Gruman and the J. Craig Venter Institute to enhance the utility of the Influenza Research Database (www.fludb.org), a NIH-supported web-based database for influenza research.
The Baumgarth lab uses two mouse infectious disease models: Infections with influenza virus and infections with Borrelia burgdorferi, a bacterial spirochete and the causative agent of Lyme disease. The influenza infection models serve as an outstanding example of how highly protective B cell responses are induced. That immune response is used to identify the innate and adaptive immune regulators that control the induction and maintenance of the highly protective antibody responses to influenza. In contrast, following infection of mice with Borrelia burgdorferi, an immune response is induced, but the bacteria cannot be cleared, likely because evolutionary adaptation has allowed this spirochete to establish persistence in mice, without causing overt disease. The Baumgarth lab has published previously that they find great abnormalities in the B cell response, most importantly, a lack of long-term adaptive immunity. Current studies are aimed at understanding the reasons for this lack of long-term immune induction, studying both the antibody responses as well as the function of CD4 T cells.
Innate-like B cells
While T and B cells are a central part of the adaptive immune system, a small subset of B cells, termed B-1 cells, is considered an "innate-like" lymphocyte. This is because B-1 cells express aspects of the adaptive immune system (an antigen-receptor that relies of gene-rearrangement) and the innate immune system (rapid responses to innate signals, a BCR that responds to pathogen-associated molecular patterns). B-1 cells are responsible for spontaneously secreting natural IgM antibodies that can bind to influenza, even in the absence of prior exposure to this virus, or with any other bacteria or viruses. The Baumgarth lab is interested in identifying the mechanisms by which these B cells generate antibodies without stimulation by foreign antigens. They are also interested in identifying the unique functions of IgM during influenza infection and during infection with B. burgdorferi by studying the interaction of IgM with its unique receptor expressed on B cells.