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Targeting antigens to CD180 rapidly induces antigen-specific IgG, affinity maturation, and immunological memory

Antigen (Ag) targeting is an efficient way to induce immune responses. Ag is usually coupled to an antibody (Ab) specific for a receptor expressed on dendritic cells (DCs), and then the Ag–anti-receptor is inoculated with an adjuvant. Here we report that targeting Ag to a receptor expressed on both...

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Detalles Bibliográficos
Autores principales: Chaplin, Jay W., Chappell, Craig P., Clark, Edward A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3782047/
https://www.ncbi.nlm.nih.gov/pubmed/24019553
http://dx.doi.org/10.1084/jem.20130188
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author Chaplin, Jay W.
Chappell, Craig P.
Clark, Edward A.
author_facet Chaplin, Jay W.
Chappell, Craig P.
Clark, Edward A.
author_sort Chaplin, Jay W.
collection PubMed
description Antigen (Ag) targeting is an efficient way to induce immune responses. Ag is usually coupled to an antibody (Ab) specific for a receptor expressed on dendritic cells (DCs), and then the Ag–anti-receptor is inoculated with an adjuvant. Here we report that targeting Ag to a receptor expressed on both B cells and DCs, the TLR orphan receptor CD180, in the absence of adjuvant rapidly induced IgG responses that were stronger than those induced by Ag in alum. Ag conjugated to anti-CD180 (Ag-αCD180) induced affinity maturation and Ab responses that were partially T cell independent, as Ag-specific IgGs were generated in CD40- and T cell–deficient mice. After preimmunization with Ag-αCD180 and boosting with soluble Ag, both WT and CD40 knockout (KO) mice rapidly produced Ag-specific IgG-forming cells, demonstrating that Ag–anti-CD180 induces immunological memory. The potent adjuvant effect of Ag-αCD180 required Ag to be coupled to anti-CD180 and the responsive B cells to express both CD180 and an Ag-specific B cell receptor. Surprisingly, CD180 Ag targeting also induced IgG Abs in BAFF-R KO mice lacking mature B cells and in mice deficient in interferon signaling. Targeting Ag to CD180 may be useful for therapeutic vaccination and for vaccinating the immune compromised.
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spelling pubmed-37820472014-03-23 Targeting antigens to CD180 rapidly induces antigen-specific IgG, affinity maturation, and immunological memory Chaplin, Jay W. Chappell, Craig P. Clark, Edward A. J Exp Med Article Antigen (Ag) targeting is an efficient way to induce immune responses. Ag is usually coupled to an antibody (Ab) specific for a receptor expressed on dendritic cells (DCs), and then the Ag–anti-receptor is inoculated with an adjuvant. Here we report that targeting Ag to a receptor expressed on both B cells and DCs, the TLR orphan receptor CD180, in the absence of adjuvant rapidly induced IgG responses that were stronger than those induced by Ag in alum. Ag conjugated to anti-CD180 (Ag-αCD180) induced affinity maturation and Ab responses that were partially T cell independent, as Ag-specific IgGs were generated in CD40- and T cell–deficient mice. After preimmunization with Ag-αCD180 and boosting with soluble Ag, both WT and CD40 knockout (KO) mice rapidly produced Ag-specific IgG-forming cells, demonstrating that Ag–anti-CD180 induces immunological memory. The potent adjuvant effect of Ag-αCD180 required Ag to be coupled to anti-CD180 and the responsive B cells to express both CD180 and an Ag-specific B cell receptor. Surprisingly, CD180 Ag targeting also induced IgG Abs in BAFF-R KO mice lacking mature B cells and in mice deficient in interferon signaling. Targeting Ag to CD180 may be useful for therapeutic vaccination and for vaccinating the immune compromised. The Rockefeller University Press 2013-09-23 /pmc/articles/PMC3782047/ /pubmed/24019553 http://dx.doi.org/10.1084/jem.20130188 Text en © 2013 Chaplin et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Article
Chaplin, Jay W.
Chappell, Craig P.
Clark, Edward A.
Targeting antigens to CD180 rapidly induces antigen-specific IgG, affinity maturation, and immunological memory
title Targeting antigens to CD180 rapidly induces antigen-specific IgG, affinity maturation, and immunological memory
title_full Targeting antigens to CD180 rapidly induces antigen-specific IgG, affinity maturation, and immunological memory
title_fullStr Targeting antigens to CD180 rapidly induces antigen-specific IgG, affinity maturation, and immunological memory
title_full_unstemmed Targeting antigens to CD180 rapidly induces antigen-specific IgG, affinity maturation, and immunological memory
title_short Targeting antigens to CD180 rapidly induces antigen-specific IgG, affinity maturation, and immunological memory
title_sort targeting antigens to cd180 rapidly induces antigen-specific igg, affinity maturation, and immunological memory
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3782047/
https://www.ncbi.nlm.nih.gov/pubmed/24019553
http://dx.doi.org/10.1084/jem.20130188
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