Cutting Edge: C3d Functions as a Molecular Adjuvant in the Absence of CD21/35 Expression

• Published in: The Journal of immunology (1950) 2004-05, Vol.172 (10), p.5833-5837
• Main Authors: Haas, Karen M, Toapanta, Franklin R, Oliver, Julie A, Poe, Jonathan C, Weis, John H, Karp, David R, Bower, Joseph F, Ross, Ted M, Tedder, Thomas F
• Format: Article
• Language: English
• Subjects: Adjuvants, Immunologic - administration & dosage; Adjuvants, Immunologic - physiology; Animals; Antibodies, Bacterial - biosynthesis; Bacterial Vaccines - administration & dosage; Bacterial Vaccines - immunology; Complement C3d - administration & dosage; Complement C3d - physiology; HIV Antibodies - biosynthesis; HIV Envelope Protein gp120 - administration & dosage; HIV Envelope Protein gp120 - immunology; HIV-1 - immunology; Immunization, Secondary; Injections, Intravenous; Mice; Mice, Inbred C57BL; Mice, Knockout; Receptors, Complement 3b - deficiency; Receptors, Complement 3b - genetics; Receptors, Complement 3b - physiology; Receptors, Complement 3d - deficiency; Receptors, Complement 3d - genetics; Receptors, Complement 3d - physiology; Streptavidin - administration & dosage; Streptavidin - immunology; Vaccines, Combined - administration & dosage; Vaccines, Combined - immunology; Vaccines, DNA - administration & dosage; Vaccines, DNA - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.172.10.5833

Complement component C3 covalently attaches to Ags following activation, where the C3d cleavage fragment can function as a molecular adjuvant to augment humoral immune responses. C3d is proposed to exert its adjuvant-like activities by targeting Ags to the C3d receptor (CD21/35) expressed by B cells and follicular dendritic cells. To directly assess the importance of CD21/35 in mediating the immunostimulatory effects of C3d, CD21/35-deficient (CD21/35(-/-)) mice were immunized with streptavidin (SA), SA-C3dg tetramers, recombinant HIV gp120 (gp120), or gp120 fused with linear multimers of C3d. Remarkably, SA- and gp120-specific Ab responses were significantly augmented in CD21/35(-/-) mice when these Ags were complexed with C3d in comparison to Ag alone. In fact, primary and secondary Ab responses and Ab-forming cell responses of CD21/35(-/-) mice approached those of wild-type mice immunized with SA-C3dg and gp120-C3d. Thus, C3d can function as a molecular adjuvant in the absence of CD21/35 expression.