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

• Published in: The Journal of clinical investigation Vol. 123; no. 7; pp. 3074 - 3083
• Main Authors: Macauley, Matthew S., Pfrengle, Fabian, Rademacher, Christoph, Nycholat, Corwin M., Gale, Andrew J., von Drygalski, Annette, Paulson, James C.
• Format: Journal Article
• Language: English
• Published: United States American Society for Clinical Investigation 01.07.2013
• Subjects: Animals; Antibodies; Antigens; Apoptosis; Autoimmunity; B-Lymphocytes - immunology; Calcium Signaling; Factor VIII - immunology; Factor VIII - therapeutic use; Hemophilia A - drug therapy; Hemophilia A - immunology; Humans; Immune Tolerance; Ligands; Liposomes - immunology; Lymphocyte Activation; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Physiological aspects; Properties; Sialic Acid Binding Ig-like Lectin 2 - agonists; Sialic Acid Binding Ig-like Lectin 2 - physiology; Sialic Acids - immunology; T cells; Viral antibodies
• ISSN: 0021-9738; 1558-8238; 1558-8238
• DOI: 10.1172/JCI69187

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.