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    • Albert Einstein College of Medicine: Doctoral Dissertations
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    • Albert Einstein College of Medicine (AECOM)
    • Albert Einstein College of Medicine: Doctoral Dissertations
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    How B cells function in the immune response to Mycobacterium tuberculosis

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    Date
    2012
    Author
    Kozakiewicz, Lee
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    Abstract
    The significance of cell-mediated immune responses in anti-tuberculosis immunity has been well characterized, but the role of humoral immunity in the host response to Mycobacterium tuberculosis is poorly understood. Recent evidence, however, has illuminated how B cells, through interactions with the cellular immune response, can regulate disease outcome and inflammatory progression during M. tuberculosis infection. We hypothesized that B cells influence the host defense against M. tuberculosis by regulating T cell responses, producing immunoglobulins, producing cytokines, and acting as antigen-presenting cells.;Using flow cytometry, we observed elevated neutrophilia and an enhanced Th17/IL-17 response in the lungs of B cell-deficient mice. Lung neutrophilia in TB-infected B cell-deficient mice could be significantly reversed by IL-17 neutralization. With recent studies reporting that neutrophilia may attenuate anti-TB vaccine efficacy, we used B cell-deficient mice to examine if B cells can modulate BCG-induced Th1 immunity. The splenic Th1 response was attenuated in B cell-deficient mice immunized with BCG. Additionally, we observed that B cell deficiency results in an enhanced local neutrophilic response and impaired T cell priming in the draining lymph nodes following immunization. Although IL-17 neutralization resulted in opposing effects on the BCG-elicited Th1 response between mouse strains, neutrophil depletion resulted in enhanced priming of Th1 cells in the draining lymph nodes of both strains. These results indicate that B cells can regulate neutrophilia by modulating the IL-17 response during M. tuberculosis infection and BCG immunization.;Previous work has uncovered potential roles for immunoglobulins in modulating TB immunity. We observed that passive transfer of immune sera derived from M. tuberculosis-infected wildtype animals reversed the lung neutrophilia/IL-17 phenotypes seen in B cell-deficient mice. B cell-deficient JhD mice and immunoglobulin-deficient mIgM mice exhibited enhanced susceptibility to infection, exacerbated disease progression, elevated lung neutrophil recruitment, increased numbers of lung Th17 cells, and increased production of pulmonary IL-10 following infection. Mice deficient in specific immunoglobulins exhibited enhanced susceptibility to infection, indicating that both IgM and IgG regulate disease progression during M. tuberculosis infection. A more thorough understanding of how B cells function during M. tuberculosis infection will allow for the development of novel strategies to enhance vaccine efficacy.
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    https://ezproxy.yu.edu/login?url=http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqm&rft_dat=xri:pqdiss:3535990
    https://hdl.handle.net/20.500.12202/1364
    Citation
    Source: Dissertation Abstracts International, Volume: 74-05(E), Section: B.;Advisors: John Chan Committee members: Theresa DiLorenzo; Marta Feldmesser; Michelle Larsen; Liise-Anne Pirofski; Steven Porcelli.
    *This is constructed from limited available data and may be imprecise.
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