Cutting edge: C3d functions as a molecular adjuvant in the absence of CD21/35 expression.
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.
Haas
Karen M
KM
Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA.
Toapanta
Franklin R
FR
Oliver
Julie A
JA
Poe
Jonathan C
JC
Weis
John H
JH
Karp
David R
DR
Bower
Joseph F
JF
Ross
Ted M
TM
Tedder
Thomas F
TF
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000502:physiology*; D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000276:immunology; D015933:Complement C3d / Q000008:administration & dosage / Q000502:physiology*; D015483:HIV Antibodies / Q000096:biosynthesis; D015699:HIV Envelope Protein gp120 / Q000008:administration & dosage / Q000276:immunology; D015497:HIV-1 / Q000276:immunology; D007117:Immunization, Secondary; D007275:Injections, Intravenous; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017463:Receptors, Complement 3b / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D017464:Receptors, Complement 3d / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D019809:Streptavidin / Q000008:administration & dosage / Q000276:immunology; D017778:Vaccines, Combined / Q000008:administration & dosage / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology
D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D001428:Bacterial Vaccines; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D017463:Receptors, Complement 3b; D017464:Receptors, Complement 3d; D017778:Vaccines, Combined; D019444:Vaccines, DNA; D015933:Complement C3d; D019809:Streptavidin