Antigenic liposomes displaying CD22 ligands induce antigen-specific B cell apoptosis
Matthew S. Macauley, … , Annette von Drygalski, James C. Paulson
Matthew S. Macauley, … , Annette von Drygalski, James C. Paulson
Published June 3, 2013
Citation Information: J Clin Invest. 2013;123(7):3074-3083. https://doi.org/10.1172/JCI69187.
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Research Article

Antigenic liposomes displaying CD22 ligands induce antigen-specific B cell apoptosis

Abstract

Antibodies confer humoral immunity but can also be harmful when they target an autoantigen, alloantigen, allergen, or biotherapeutic. New strategies are needed for antigen-specific suppression of undesired antibody responses, particularly to T cell–dependent protein antigens, because they elicit T cell help. Here we show that liposomal nanoparticles, displaying both antigen and glycan ligands of the inhibitory coreceptor CD22, induce a tolerogenic program that selectively causes apoptosis in mouse and human B cells. These SIGLEC-engaging tolerance-inducing antigenic liposomes (STALs, where SIGLEC is defined as sialic acid–binding Ig-like lectin) induced robust antigen-specific tolerance to protein antigens in mice, preventing subsequent immune response to challenge with the same antigen. Since development of inhibitory antibodies to FVIII is a serious problem in treatment of hemophilia A patients, we investigated the potential of this approach for inducing tolerance to FVIII in a hemophilia mouse model. STALs prevented formation of inhibitory FVIII antibodies, allowing for effective administration of FVIII to hemophilia mice to prevent bleeding. These findings suggest that STALs could be used to eliminate or prevent harmful B cell–mediated immune responses.

Authors

Matthew S. Macauley, Fabian Pfrengle, Christoph Rademacher, Corwin M. Nycholat, Andrew J. Gale, Annette von Drygalski, James C. Paulson

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Figure 1

Induction of tolerance with liposomes displaying antigen and CD22 ligands.

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Induction of tolerance with liposomes displaying antigen and CD22 ligand...
(A) Schematic of STALs. (B) Chemical structures of CD22 ligands used for studies in mice. (C and D) CD22-dependent induction of tolerance to a T-independent (NP; C) and a T cell–dependent antigen (HEL; D). WT or Cd22-KO mice were treated on day 0 (white arrow) as shown and challenged with the immunogenic liposomes on days 15 and 30 (black arrow). Data represent mean ± SEM. (n = 8–10). (E) Titration of BPANeuGc and NeuGc on STALs. Titers were determined after 2 challenges with immunogenic liposomes on days 15 and 30 (n = 4). (F) Mice were tolerized to HEL at different times relative to the challenge and titers were determined 2 weeks after challenge with immunogenic liposomes and are plotted as percentage relative to immunization of naive mice (n = 4). Data represent mean ± SEM. (n = 4).