Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adjuvants, Immunologic / administration & dosage
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Adjuvants, Immunologic / physiology*
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Animals
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Antibodies, Bacterial / biosynthesis
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Bacterial Vaccines / administration & dosage
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Bacterial Vaccines / immunology
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Complement C3d / administration & dosage
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Complement C3d / physiology*
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HIV Antibodies / biosynthesis
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HIV Envelope Protein gp120 / administration & dosage
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HIV Envelope Protein gp120 / immunology
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HIV-1 / immunology
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Immunization, Secondary
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Injections, Intravenous
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Receptors, Complement 3b / deficiency*
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Receptors, Complement 3b / genetics*
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Receptors, Complement 3b / physiology
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Receptors, Complement 3d / deficiency*
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Receptors, Complement 3d / genetics*
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Receptors, Complement 3d / physiology
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Streptavidin / administration & dosage
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Streptavidin / immunology
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Vaccines, Combined / administration & dosage
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Vaccines, Combined / immunology
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Vaccines, DNA / administration & dosage
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Vaccines, DNA / immunology
Substances
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Adjuvants, Immunologic
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Antibodies, Bacterial
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Bacterial Vaccines
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HIV Antibodies
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HIV Envelope Protein gp120
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Receptors, Complement 3b
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Receptors, Complement 3d
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Vaccines, Combined
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Vaccines, DNA
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Complement C3d
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Streptavidin