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Natural Killer Cell Regulation of Humoral Immunity

Rydyznski, Carolyn E
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1535377157934852

Abstract Details

2018, PhD, University of Cincinnati, Medicine: Immunology.
Natural killer (NK) cells are innate lymphocytes well regarded for their role in direct killing of virally-infected or transformed cells. However, there is increasing evidence to suggest that NK cells are also potent regulators of adaptive immune responses. Our lab previously demonstrated that NK cells can kill activated CD4+ T cells following viral infection, thereby limiting the expansion of antigen specific CD8+ T cells. However, not only are CD4+ T cells vital to CD8+ T cell functions, but a subset of CD4+ T cells named follicular helper T (TFH) cells are also necessary for optimal humoral immunity. Thus, we sought to determine whether NK cells might regulate CD4+ TFH cells following infection or immunization, and what consequences this might hold for the overall humoral response. Crucial for humoral immunity is the germinal center (GC) reaction, a specialized structure within secondary lymphoid tissues in which germinal center B cells engage in complex crosstalk with TFH cells. It is this cross talk which facilitates affinity maturation and class switching of the B cell receptor and ultimately promotes B cell differentiation to antibody secreting plasma cells or memory B cells. Our studies demonstrate that NK cells do indeed suppress the expansion of CD4+ TFH cells following viral or protein-based immunization regimens in a perforin-dependent manner. This suppression of TFH cell expansion in the presence of NK cells also results in decreased numbers of GC B cells, circulating immunoglobulin and antibody secreting cells. Additionally, NK cell suppression of GC expansion also correlates with decreased affinity maturation of antigen-specific GC B cells. Together, our findings highlight a previously underappreciated role for NK cells in regulating humoral responses and suggest that modulation of NK cell function at the time of vaccination could provide a novel means of bolstering humoral immunity.
Stephen Waggoner, Ph.D. (Committee Chair)
Fred Finkelman, M.D. (Committee Member)
David Hildeman, Ph.D. (Committee Member)
Kimberly Risma, M.D. (Committee Member)
Harinder Singh, Ph.D. (Committee Member)
192 p.
Immunology
natural killer cell; germinal center; humoral immunity; follicular helper T cell; immunization

Recommended Citations

Citations

  • Rydyznski, C. E. (2018). Natural Killer Cell Regulation of Humoral Immunity [Doctoral dissertation, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1535377157934852

    APA Style (7th edition)

  • Rydyznski, Carolyn. Natural Killer Cell Regulation of Humoral Immunity. 2018. University of Cincinnati, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1535377157934852.

    MLA Style (8th edition)

  • Rydyznski, Carolyn. "Natural Killer Cell Regulation of Humoral Immunity." Doctoral dissertation, University of Cincinnati, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1535377157934852

    Chicago Manual of Style (17th edition)

ucin1535377157934852
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This open access ETD is published by University of Cincinnati and OhioLINK.