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

• Published in: The Journal of experimental medicine Vol. 210; no. 10; pp. 2135 - 2146
• Main Authors: Chaplin, Jay W, Chappell, Craig P, Clark, Edward A
• Format: Journal Article
• Language: English
• Published: United States The Rockefeller University Press 23.09.2013
• Subjects: Animals; Antibody Affinity - immunology; Antibody Formation - immunology; Antigens - immunology; Antigens - metabolism; Antigens, CD - immunology; Antigens, CD - metabolism; B-Lymphocytes - immunology; B-Lymphocytes - metabolism; CD40 Ligand - metabolism; Epitopes - immunology; Epitopes - metabolism; Germinal Center - immunology; Germinal Center - metabolism; Histocompatibility Antigens Class II - immunology; Immunoglobulin G - immunology; Immunoglobulin G - metabolism; Immunologic Memory; Interferon-alpha - metabolism; Interferon-beta - metabolism; Interleukin-4 - metabolism; Lymphocyte Activation - immunology; Mice; Mice, Knockout; Protein Binding - immunology; Receptors, Antigen, B-Cell - immunology; Receptors, Antigen, B-Cell - metabolism; Signal Transduction
• ISSN: 0022-1007; 1540-9538
• DOI: 10.1084/jem.20130188

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.