Copresentation of antigen and ligands of Siglec-G induces B cell tolerance independent of CD22

• Author(s) / Creator(s)

  • Pfrengle, F.
  • Kawasaki, N.
  • Paulson, J. C.
  • Macauley, M. S.

• Differentiation of self from nonself is indispensable for maintaining B cell tolerance in peripheral tissues. CD22 and Siglec-G (sialic acid-binding Ig-like lectin G) are two inhibitory coreceptors of the BCR that are implicated in maintenance of tolerance to self Ags. Enforced ligation of CD22 and the BCR by a nanoparticle displaying both Ag and CD22 ligands induces a tolerogenic circuit resulting in apoptosis of the Ag-reactive B cell. Whether Siglec-G also has this property has not been investigated in large part owing to the lack of a selective Siglec-G ligand. In this article, we report the development of a selective high-affinity ligand for Siglec-G and its application as a chemical tool to investigate the tolerogenic potential of Siglec-G. We find that liposomal nanoparticles decorated with Ag and Siglec-G ligand inhibit BCR signaling in both B1 and B2 B cells compared with liposomes displaying Ag alone. Not only is inhibition of B cell activation observed by ligating the BCR with Siglec-G, but robust tolerance toward T-independent and T-dependent Ags is also induced in mice. The ability of Siglec-G to inhibit B cell activation equally in both B1 and B2 subsets is consistent with our observation that Siglec-G is expressed at a relatively constant level throughout numerous B cell subsets. These results suggest that Siglec-G may contribute to maintenance of B cell tolerance toward self Ags in various B cell compartments.

• Date created

  2013

• Subjects / Keywords

  • Cd22-Deficient Mice
  • In-Vivo
  • Signal-Transduction
  • Selection
  • Tissue-Specific Expression
  • Activation
  • Survival
  • Negative Regulator
  • Immune-System
  • Inhibitory Receptors

• Type of Item

  Article (Published)

• DOI

  https://doi.org/10.7939/R3X63BK82

• License

  © 2013 F. Pfrengle 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.