Exosomes from Bone Marrow Dendritic Cells Pulsed with Diphtheria Toxoid Preferentially Induce Type 1 Antigen-Specific IgG Responses in Naive Recipients in the Absence of Free Antigen

• Published in: Journal of Immunology Vol. 177; no. 6; pp. 3757 - 3762
• Main Authors: Colino, Jesus, Snapper, Clifford M
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 15.09.2006
• Subjects: Animals; Antibodies, Bacterial - biosynthesis; Antibodies, Bacterial - classification; Bone Marrow Cells - cytology; Bone Marrow Cells - immunology; Bone Marrow Cells - microbiology; Cattle; Cell Polarity - immunology; Cells, Cultured; Dendritic Cells - cytology; Dendritic Cells - immunology; Dendritic Cells - microbiology; Diphtheria Toxoid - immunology; Diphtheria Toxoid - metabolism; Drug Contamination; Epitopes - biosynthesis; Female; Immunoglobulin G - biosynthesis; Immunoglobulin G - classification; Immunoglobulin Isotypes - biosynthesis; Interleukin-12 - analysis; Interleukin-6 - analysis; Mice; Mice, Inbred BALB C; Transport Vesicles - immunology; Transport Vesicles - metabolism; Transport Vesicles - microbiology
• ISSN: 0022-1767; 1550-6606; 1365-2567
• DOI: 10.4049/jimmunol.177.6.3757

Exosomes derived from dendritic cells (DC) activate T cells in vivo, but whether exosomes are able to induce and/or modulate humoral immune responses is still unknown. We show that murine bone marrow DC pulsed in vitro with an intact protein (diphtheria toxoid (DT)) produce exosomes that induce, in the absence of free protein, in vivo Ig responses specific for DT in naive recipients. Furthermore, these exosomes stimulate secondary IgG anti-DT responses in mice primed with intact DT. Exosomes from mature, relative to immature, DC were more effective at inducing primary, although not secondary, IgG anti-DT responses. Whereas intact DT preferentially induced a type 2 (IgG1) anti-DT response, exosomes from DT-pulsed bone marrow DC favored induction of type 1 (IgG2b and IgG2a) DT-specific IgG. These results are the first to demonstrate the ability of exosomes derived from Ag-pulsed DC to induce and modulate Ag-specific humoral immunity in vivo.