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Siglecs induce tolerance to cell surface antigens by BIM-dependent deletion of the antigen-reactive B cells

  • Author(s) / Creator(s)
  • Infusion of blood cells from a donor can induce humoral tolerance in a recipient and increase the probability of successful organ transplant, a clinical method defined as donor-specific transfusion (DST). Despite the clinical success of DST, the immunological mechanisms by which blood cells displaying a foreign Ag induce tolerance remain poorly understood. Based on recent findings showing that the B cell siglecs, CD22 and Siglec-G, can promote tolerance to Ags presented on the same surface as their ligands, we speculated that the B cell siglecs are key players in tolerance induced by DST. Using a variety of chemical and genetic approaches, we show that the B cell siglecs mediate tolerance to cell surface Ags by initiating an inhibitory signal that culminates in elimination of the Ag-reactive B cell. CD22 and Siglec-G are recruited to the immunological synapse by sialic acid ligands on the Ag-bearing cells, producing a tolerogenic signal involving Lyn and the proapoptotic factor BIM that promotes deletion of the B cell and failure of mice to develop Abs to the Ag upon subsequent challenge. We speculate that this tolerogenic mechanism is a contributing factor in DST and a mechanism of peripheral B cell tolerance to cell surface autoantigens.

  • Date created
    2014
  • Subjects / Keywords
  • Type of Item
    Article (Published)
  • DOI
    https://doi.org/10.7939/R35Q4S161
  • License
    © 2014 M. S. Macauley et al. This version of this article is open access and can be downloaded and shared. The original author(s) and source must be cited.
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  • Citation for previous publication
    • Macauley, M. S., & Paulson, J. C. (2014). Siglecs induce tolerance to cell surface antigens by BIM-dependent deletion of the antigen-reactive B cells. The Journal of Immunology, 193(9), 4312-4321. https://doi.org/10.4049/jimmunol.1401723
  • Link to related item
    https://doi.org/10.4049/jimmunol.1401723