Maintenance of peripheral B cell tolerance to self-antigens is still poorly understood and of high interest with respect to the roles of B cells in autoimmune diseases.  The B cell receptor is highly regulated by co-receptors that have the potential to aid in distinguishing between 'self' and 'non-self' and minimize inappropriate activation to self-antigens.  B cell siglecs, CD22 and Siglec-G/10, are unique among inhibitory co-receptors by their recognition of sialic acid-containing glycans as 'self'.  Previously we showed that multivalent presentation of high affinity CD22 ligands in cis with a T-independent antigen can induce tolerance to B cells (Duong et al., J. Exp. Med., 2010). We have now developed high affinity ligands selective for CD22 and Siglec-G to investigate their respective roles in induction of B cell tolerance. By covalent attachment to lipids, the ligands can be readily incorporated into antigen bearing liposomal nanoparticles for co-presentation to B cells.  Using this platform, robust B cell tolerance is achieved towards both T-independent and T-dependent antigens in mice.  Mechanistic studies demonstrate that CD22 and Siglec-G act cooperatively to maintain peripheral B cell tolerance by recognition of sialic acid-containing glycans as 'self' that are expressed on all mammlian cells. This platform has potential for antigen specific tolerization of B cells in a therapeutic setting. (NIH grants AI050143, AI099141, CA013889 and HFSP Fellowship LT001099/2010-L)

Siglec-ligand decorated nanoparticles for induction of B cell tolerance

244th National Meeting (2012)

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