The role of apoptotic cells in the breakdown of B cell tolerance Public Deposited

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Last Modified
  • March 21, 2019
Creator
  • Krum, Kristen N.
    • Affiliation: School of Medicine, Department of Microbiology and Immunology
Abstract
  • We have recently shown that dendritic cells (DCs) and macrophages (MΦs) are able to produce IL-6, sCD40L, and TNFα that regulate autoreactive B cells with an anergic phenotype. In systemic lupus erythematosus (SLE) autoreactive B cells are dysregulated allowing for their activation, autoantibody production, and loss of susceptibility to DC/MΦ-mediated regulation. Apoptotic cells have been found to contribute to dysregulation and disease pathogenesis in SLE patients and lupus-prone mice, such as MerTKkd or lpr mice. We hypothesized that if an apoptotic cell burden is responsible for dysregulation of autoreactive B cells, then removal of the apoptotic cell burden by injected C57BL/6 DCs and MΦs should restore susceptibility of autoreactive B cells to DC/MΦ-mediated regulation. We found that autoreactive B cells from mice with clearance defects, MerTKkd and lpr, were not susceptible to DC/MΦ-mediated regulation. Injecting C57BL/6 DCs and MΦs into 2-12H/lpr mice restored autoreactive B cells to be susceptible to CD40L and increased basal pERK levels, while not reducing the apoptotic cell burden in the spleen. Also, DC/MΦ-treated 2-12H/lpr mice reduced autoantibody levels. In DC/MΦ treated B6/lpr mice, susceptibility to IL-6 was restored in autoreactive B cells, but there was no change in apoptotic cell burden in the spleen. In addition, autoantibody production by B6/lpr mice was not affected by DC/MΦ treatment. Further optimization of apoptotic cell removal and autoantibody production could make DC/MΦ injection a potential therapeutic for SLE.
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  • In Copyright
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  • "... in partial fulfillment of the requirements for the degree of Masters in Science in the Department of Microbiology and Immunology"
Advisor
  • Vilen, Barbara J.
Degree granting institution
  • University of North Carolina at Chapel Hill
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Place of publication
  • Chapel Hill, NC
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  • Open access
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