Dendritic Cell and Macrophage-Mediated Tolerance in Lupus-Prone Mice

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  • March 20, 2019
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  • Gilbert, Mileka Richelle
    • Affiliation: School of Medicine, Department of Microbiology and Immunology
Abstract
  • During infection, immune cells respond to polyclonal activators, like bacterial and viral antigens, through innate immune responses. Therefore, mechanisms to regulate the activation of autoreactive B cells during polyclonal activation are necessary to prevent autoimmunity. Previous studies into the mechanisms of B cell tolerance have focused on B cell Receptor (BCR)-mediated regulation of autoreactive or chronically antigen-experienced B cells. However, the regulation of chronically antigen-experienced B cells during polyclonal activation is less understood. We recently identified a novel mechanism of tolerance wherein DCs and MΦs repress Ig secretion by autoreactive B cells. Polyclonal activators through Toll-like Receptors (TLRs) induce DCs and MΦs to secrete soluble factors (IL-6, sCD40L, and TNFα) that differentially regulate naïve and chronically antigen-experienced B cells. IL-6, sCD40L, and TNFα selectively repress chronically stimulated autoreactive B cells while having no effect on naïve B cells. Thus, we have identified a mechanism that prevents autoimmunity while allowing naïve B cells to respond during innate immune responses. Significantly, TLR-activated DCs and MΦs from lupus-prone mice are defective in repressing autoreactive B cells, coincident with defects in IL-6, sCD40L, and TNFα secretion. This could allow autoreactive B cells to secrete autoantibodies during innate immune responses, promoting autoimmune disease in lupus-prone mice. Determining the TLR defect in DCs and MΦs from lupus-prone mice could identify a genetic signature for individuals susceptible to lupus disease.
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  • In Copyright
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  • Vilen, Barbara J.
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  • Open access
Date uploaded
  • October 19, 2010

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